Control of COVID-19

Martin L. Nelwan, PhD

Nelwan Institution for Human Resource Development
Department of Animal Science – Other
Jl. A. Yani No. 24, Palu 94111, Indonesia
E-mail: mlnelwan2@gmail.com

Highlights

 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease

2019 (COVID-19) .
 Diagnosis of COVID-19 can use RT-PCR, RT-LAMP, and CRISPR-based techniques
 Vaccines may include Moderna, Pfizer, and Sinovac products.
 Consumption of Curcuma longa daily can prevent COVID-19.
 Drugs can include Curcuma longa and remdesivir.

Abstract

Background: Severe acute respiratory syndrome coronavirus 2-(SARS-CoV-2) causes corona

virus disease 2019 (COVID-19). Diagnosis of this disease can consist of polymerase chain
reaction (PCR) techniques and cluster regularly interspaced short palindromic repeats (CRISPR)
based technique. Vaccines, drugs such as remdesivir, plant extracts such as Curcuma longa have
important roles for treating and preventing COVID-19.
Objectives: In this study, the author reports the progress in a study of COVID-19 focused on
SARS-CoV-2, diagnosis of COVID-19, prevention and treatment of COVID-19 as objectives of
this study.
Results: SARS-CoV-2 causes COVID-19. This disease has spread all over the world. Diagnosis
tools of COVID-19 can include such as nanopore sequencing and real time quantitative (qRT-
PCR). Vaccines can include such as Moderna, Pfizer, and Sinovac products. Current promising
drugs of COVID-19 are Curcuma longa (turmeric) and remdesivir. Curcuma longa may prevent
COVID-19 and remdesivir Other drugs may be chloroquine/hydroxychloroquine,
dexamethasone, and lopinavir/ritonavir. Turmeric can also prevent COVID-19. For treatment, it
can be taken along with remdesivir or other drug such as hydroxychloroquine.
Conclision: COVID-19 is caused by SARS-CoV-2. To detect this disease, RT-PCR, for instance,
can be used. Vaccines are such as Pfizer product. Drugs of COVID-19 include Curcuma longa
and remdesivir.

Keywords: COVID-19, hydroxychloquine, remdesivir, turmeric, SARS-CoV-2, vaccines

Introduction

Abbreviation of severe acute respiratory syndrome coronovirus 2 is SARS-CoV-2. It causes

coronovirus disease 2019 (COVID-19). China detected SARS-CoV-2 in December 2019 in
Wuhan; China.1 This disease has infected as many as 65,870,030 million people and caused

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
 1,523,583 million people deaths within a year. It has spread all over the world. In Indonesia, this
disease has infected around 569,707 people and has caused around 17,580 people deaths.2

Several diagnosis tools are available for detecting SARS-CoV-2. These include reverse-
transcription polymerase chain reaction (RT-PCR),3 real-time RT-PCR (rRT-PCR),3,4 and
reverse transcription loop-mediated isothermal amplification (RT-LAMP).3,5 In settings where
diagnostic tools are unavailable, rapid antigen detecting tests may facilitate earlier diagnosis and
required action. World Health Organization recommends a single approach to clinical diagnostic
for disease confirmation: the detection of a unique sequences of SARS-CoV-2 RNA by nucleic
acid amplification testing (NAAT) such as rRT-PCR). It calls for research to develop and
evaluate the utility of simpler, more portable detection platforms. World Health Organization
guidance also encourages the use serological surveys of antibody responses to better understand
the extent of and risk factors for COVID-19 infection through surveillance investigations to
calculate the attract rate in different populations.4

Vaccines of COVID-19 are development. More than 120 vaccine candidates worldwide are in
various preclinical and phase I to III clinical trials. These vaccine candidates include inactivated,
live-attenuated, viral-vectored replicating and non-replicating, protein- and peptide-based, and
nucleic acid approaches.6 Vaccines can very helpful protecting people from SARS-CoV-2.
However, it needs a long time to provide effective and efficacy vaccines. Plant extracts, such as
Curcuma longa (turmeric), can help protect people from COVID-19.7 Turmeric can be used in
combination with other plant extracts such as Curcuma zanthorrhiza. However, this study only
discusses the use of turmeric for treating and preventing this disease.

Drugs of COVID-19 are also under development. These include such as remdesivirr,
chloroquine/hydroxychloroquine, dexamethasone, azitthromicyn, and doxycycline.8,9 Remdesivir
has finished for clinical trial. It reduces clinical recovery time.10 All these drugs can be used in
combination with Curcuma longa for treating COVID-19.

In this study, the author reports the progress in a study of COVID-19 that focused on SARS-
CoV-2, diagnosis of COVI-19, Curcuma longa for protection and treatment of COVID-19, and
vaccines of COVID-19 as objectives of COVID-19.

Methods

The author searched Google, ScienceDirect, and the PubMed Database at National Center for
Biotechnology (NCBI) for articles on COVID-19. Articles included unrestricted free open
access, free open access articles for non-commercial, articles with permissions if required, and in
English. Publication dates of these articles were unrestricted. However, the author strengthens
the latest publication of these articles. Keywords used for searches of articles included:

SARS-CoV-2
Genetic of SARS-CoV-2
Transmission of COVID-19
Spread of COVID-19
Diagnosis of COVID-19

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 Drugs of COVID-19
Drug developments of COVID-19
Plant extracts for COVID-19
Curcuma longa and COVID-19
Treatment of COVID-19
Chloroquine/hydroxychloroquine and COVID-19
Dexamethasone and COVID-19
Lopinavir/ritonavir and COVID-19
Remdesivir and COVID-19
Vaccines of COVID-19
Vaccine developments of COVID-19
Prevention of COVID-19

Severe acute respiratory syndrome coronavirus 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19.3,5 It belongs

to the subfamily Orthocoronavirinae, in the family Coronaviridae,6 group 2 betacoronavirus.6,11
Six types of coronaviruses can infect humans. These include alpha coronaviruses HCoV-229E
and HCoV-NL63, and betacoronaviruses HCoV-OC43, HCoV-HKU1, SARS-CoV-1, and
Middle Eastern respiratory syndrome (MERS) coronavirus.5,6 Severe acute respiratory syndrome
CoV-2 and MERS-coronavirus are highly transmissible and pathogenic. These two viruses are
associated high morbidity and mortality rate in humans.6

Phylogenetic analysis shows that SARS-CoV-2 spread to humans through transmission from
wild animals illegally sold in Huanan Seafood Wholesale Market in Wuhan, China.3 The
coronavirus genome is a single stranded RNA of about 30 kilo bases, the largest among the RNA
viruses. Coronaviruses usually infect their hosts in a species-specific manner, resulting in acute
or persistent infections. The RNA genome contains a 5ʹ cup and 3ʹ poly-A tail. It makes the RNA
genome suitable for direct translation into a large size poly-protein. Structural protein occupies
10-kilo bases of the genome, whereas non-structural protein occupies two-third of the genome.
The coronavirus has a spherical shape with a diameter of approximately 125 nanometers. The
most striking feature of the coronavirus is the club-shaped spike protein projecting from the
virion surface. These spike proteins serve as attachment proteins for the virus to enter host cells.
1

The SARS-CoV-2 genome sequence shares about 80% sequence identity with SARS-CoV-1 and
shares about 50% identity with MERS-CoV. This virus genome consists of 14 open reading
frames (ORFs). Two-thirds of ORFs encode 16 non-structural proteins (nsp 1-16) that make up
the replicate complex. One-third encodes nine accessory proteins (ORF) and four structural
proteins: envelope (E), membrane (M), nucleocapsid (N), and spike (S). Spike mediates SARS-
CoV entry into host cells. However, the S gene of SARS-CoV-2 is highly variable from SARS-
CoV. It shares less than 75% nucleotide identity. Spike gene has a receptor-binding domain
(RBD). It mediates direct contact with the angiotensis-converting enzyme 2 (ACE2), a cellular
receptor. In addition, S gene has an S1/S2 polybasic cleavage site. It is proteolytically cleaved by
cellular cathepsin L and the transmembrane protease serine 2 (TMPRSS2). The transmembrane
protease serine 2 facilitates viral entry at the plasma membrane surface. Moreover, cathepsin L

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 activates SARS-CoV-2 S in endosomes and can compensate for entry into cells that lack
TMPRSS2. Once the genome is released into the host cytosol, ORF1a and ORF1b are translated
into viral replicate proteins. These proteins cleave into individual nasps. These cleavages are
through host and viral protease, the PLpro. Viral replicase proteins form the RNA-dependent
RNA polymerase, nsp12 derived from ORF1b. Then, replicate components rearrange the
endoplasmic reticulum (ER) into double-membrane vehicles (DMVs). Double-membrane
vehicles facilitate viral replication of genomic and sub genomic RNAs (sgRNA). Sub genomic
RNAs are translated into accessory and viral structural proteins. Either accessory or viral
structural proteins facilitate formation of virus particle.11

The ACE2 is differentially expressed in many human tissues. These include colon (colonocytes),
kidney (proximal tubules), liver (cholangiocytes), and lung (type 2 alveolor cells). Notably, the
cellular serine protease is critical for activation of the SARS-CoV-2 transmembrane Spike
glycoprotein, priming, and viral cell entry. Glycoprotein is the main target of neutralizing
antibodies, for example. Severe acute respiratory syndrome CoV-2 can invade host cells (Vero
E6 cell) through a new CD147-S protein route. The CD147 receptor-targeted antiviral might also
a beneficial therapeutic strategy on COVID-19.6

The human angiotensin-converting enzyme 2 is the common receptor SARS-CoV, SARS-CoV-

2, and NL63. However, NL63 receptor-binding domain (RBD) has a structure significantly
different from those of SARS-CoV and CoV-2. The receptor-binding domain of SARS-CoV-2
binds more strongly to the ACE2 receptor than that of SARS-CoV. It makes it a more suitable
target for the development of virus attachment inhibitors, neutralizing antibodies, and vaccines.
Strong binding of SARS-CoV-2 to ACE2 receptor is a crucial reason for the higher infection rate
in SARS-CoV-2 than MERS-CoV and SARS-CoV. However, the full-length of S protein of
SARS-CoV-2 has similar or lower affinity to human ACE2 compared to SARS-CoV. This
suggests that SARS-CoV-2 RBD is less exposed compared to SARS-CoV RBD. In addition, it
less dependent on target cell protease as it is pre-activated by proprotein convertase furin.1

Transmission of COVID-19

Transmission of SARS-CoV-2 is primarily through contact, respiratory droplets, and potential

route of fecal-oral. Reproductive number (RO) of SARS-CoV-2 is about 2.3 to 5.7, while SARS-
CoV is about 3. The mainly virus replication occurs in the mucosal epithelium of the upper
respiratory tract: nasal cavity and pharynx. Further multiplies occur in the mucosa of the lower
respiratory tract and gastrointestinal. This virus replication results in mild viremia. The
maximum propagation distance of aerosols containing SARS-CoV-2 virion is 4 meters from
patients with COVID-19. Severe acute respiratory syndrome CoV-2 aerosols remained infectious
in the tissue culture experiments, and the infectivity decreased slightly during a three-hour
observation period. The SARS_CoV-2 also exists in stool samples. Although SARS-CoV-2 may
be transmitted through the fecal oral route, these occur only on very few patients and still need
further researchers.12

Severe acute respiratory syndrome CoV-2 has rapidly spread across the globe. The rapid
transmission of SARS-CoV-2 has caused fear, panic, economic disruption, morbidity and
mortality, and significant public health concerns. Data have revealed that the clinical

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 characteristic of COVID-19 can be very heterogeneous with a broad spectrum of severity,
including illness resulting in death. Asymptomatic individuals can transmit SARS-CoV-2
infection. Individuals over 65 years old, individuals of all ages whose serious underlying medical
conditions, and those who are immunocompromised at higher risk of serious COVID-19 illness
and complications. Higher mortality occurs in older male patients than female patients.6

Early reports of patients with cough and symptom progression to severe pneumonia suggested
communicability of SARS-CoV-2 via the respiratory route. Direct transmission by respiratory
droplets is reinforced by productive SARS-CoV-2 replication in both the upper respiratory tract
(URT) and lower respiratory tract (LRT), and the increasing number of reports suggesting
human-to-human spread among close contacts exhibiting active coughing. There is no evidence
for nonsymptomatic/presymptomatic spread of SARS-CoV-2, which is in contrast to the
transmission dynamics of SARS-CoV. This finding shows the ability of SARS-CoV-2 to
colonize and replicate in the throat during early infection. It suggests that mask-wearing, contact
tracing, and physical isolation for control of COVID-19.11

The symptoms of COVID-19 are usually like a normal cold and influenza and do not become
severe. It is not the same as people with diseases such as diabetes, heart, lung and other diseases.
For these people, the disease can take on critical forms that sometimes lead to death. Some
people have no symptoms (mild pneumonia). Furthermore, patients may have severe shortness of
breath, a sore throat or severe headache. Some patients may have acute respiratory distress
syndrome, acute heart injury, and secondary infection with bacteria.12

Infection with highly pathogenic SARS-CoV-2 causes severe ‘flu’ like symptoms that can
progress to acute respiratory distress (ARDS), pneumonia, renal failure, and death.11 The most
common symptoms are fever, cough, and dyspnea,11,13,14 accounting for 83%, 82% and 31% of
patients with COVID-19, respectively. The incubation period is about five to six days. The
COVID-19 encompasses not only rapid respiratory/gastrointestinal illnesses, but can also have
long-term ramifications such as myocardial inflammation. Severe COVID-19 is not restricted to
the aged population as initially reported. Children and young adults are also at risk.11

Groups of adults with SARS-Cov-2 infection consist of asymptomatic/pre-symptomatic, mild,

moderate, severe, and critical. Asymptomatic/pre-symptomatic does not have symptoms that are
consistent with COVID-19. Mild patients have any of the various signs and symptoms. These
can include cough, diarrhea, fever, headache, loss of taste and smell, malaise, muscle pain,
nausea, sore throat, and vomiting. However, this group of patients does not have shortness of
breath, dyspnea, or abnormal chess imaging. Moderate patients show evidence of lower
respiratory during clinical assessment or imaging and have saturation of oxygen (SpO2) ≥ 94%
on room air at sea level. Severe patients have SpO2) ≤ 94% on room air at sea level, a ration
partial pressure of oxygen (PaO2/FiO2) < 300 mmHg, respiratory frequency > 30 breaths per
minute, or lung infiltrates > 50%. Finally, critical illness has respiratory failure, septic shock,
and/or multiple organ dysfunctions. Patients with comorbidities are at higher risk of progression
to severe COVID-19. Comorbidities can include patients with 65 years or older, having
cardiovascular disease, chronic lung disease, diabetes, cancer, obesity, or chronic kidney disease,
and being a recipient of immunosuppressive therapy. These patients should be monitored closely
until clinical recovery is achieved.10

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 The SARS-CoV-2 can infect humans and a small number of animals. Droplets or direct contact
can cause transmission of COVID-19 human-to-human. Diagnosis tools are important for
determining COVID-19. Many diagnosis tools are available. The following section discusses
regarding diagnosis tools for COVID-19.

Diagnosis

Rapid and initial diagnosis of COVID-19 is the focus of treatment and control. Molecular tests
are the basis for confirmation of COVID-19. However, serological tests for SARS-CoV-2 are
available and play a key role in recognizing the epidemiology of the virus and in recognizing
populations at higher risk for infection. Point-of-care tests are accurate, low cost and non-
specific device requirements, portable, and rapid. These tests provide terrific help for disease
diagnosis and detection.12

Detection techniques of SARS-CoV-2

Six detection technique platforms of SARS-CoV-2 are available, such as sequencing, polymerase
chain reaction (PCR) and immunological diagnostic (Table 1). For example, sequencing
techniques consist of MinION nanopore sequencing and nanopore sequencing. Polymerase chain
reaction techniques consist of such as droplet digital PCR (ddPCR), real time quantification PCR
(qRT-PCR), and reverse transcription loop-mediated isothermal amplification (RT-LAMP).
Immunological diagnostic consists of such as ELISA. Diagnosis tools are important for detecting
COVID-19 and even for eliminating the disease.

Sequencing

Compared with other sequencing platforms, nanopore-sequencing technology has a longer read
length and performs direct RNA sequencing. The instrument in nanopore sequencing is compact.
It has certain advantages in pathogen detection. For example, MinION nanopore sequencing
could detect a variety respiratory viruses including SARS-CoV-2 within six to ten hours.
However, the current sequencing platforms are difficult to achieve low-cost and rapid detection.
It has not been widely used in the prevention and control of this epidemic. 14

Droplet digital PCR

Among various partitioning methods, such as microwell plates and oil emulsion, droplet digital
PCR (ddPCR) is the most widely used method with commercial systems available. Droplet
digital PCR has higher sensitivity than conventional PCR5 or qRT-PCR.12. It makes it possible
for detecting very low viral loads. For example, when pharyngeal swab samples from patients
with COVID-19 who were convalescing were compared, ddPCR detected viral DNA in 64.2%
RT-PCR negative samples.5 In addition, ddPCR is more costly than qPCR for each test
performed using dedicated instruments and consumables.12 This tool detects low level of SARS-
CoV-2 RNA. It possesses all the critical characteristics that would allow its use to improve and
accelerate COVID-19 diagnosis in clinical samples.17

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 Real-time quantification RT-PCR

World Health Organization provides several real-time quantitative PCR (qRT-PCR) protocols for
detection of SARS-CoV-2. The gene targets for detecting SARS-CoV-2 are dissimilar in China
(ORF1ab and N genes), France (RdRP1 and RdRP2 targets), Germany (RdRP, E and N genes),
Japan (pancorona and multiple targets, spike protein), United States (N1, N2, N3 genes), and
Thailand (ORF1b, N genes). The Centers for Disease Control and Prevention (CDC) established
a RT-PCR panel for specific detection SARS-CoV-2 and universal detection SARS-like beta-
CoVs. Three sets of primers were for detecting the N gene. One set of primers/probes was
universally for detecting all beta-CoVs. The other two were specific for detecting SARS-CoV-2.
All three targets must be positive for confirmation of COVID-19. Charite, Germany developed
two nucleic acid tests for detecting RdRP and E genes of SARS-CoV-2, SARS-CoV, and bat-like
beta-CoVs. Both tests are positive could enter the next step of the test; these are the SARS-CoV-
2 specific RT-PCR test and RdRP gene.12

The CRISPR technique

Clustered regularly interspaced short palindromic repeats (CRISPR/Cas) systems offer new ways
to amplify analytical signal with the precision down to single-nucleotide variants. Commonly,
these assays use Cas12a (CRISPR-associated protein 12a) or Cas13a (CRIPRS-associated
protein 13a) enzymes. It exploits collateral cleavage of single-stranded DNA (Cas12a) or RNA
(Cas13a) by these nucleases. In one method, termed SHERLOCK (specific high-sensitivity
enzyme reporter unlocking), RNA targets are first amplified via reverse transcription
recombinant polymerase amplification (RT-RPA) and the amplified DNAs are transcribed to
target DNA. CRISPR RNA (crRNA)-Cas13a complex then binds and cleaves target RNA. The
complex to provide a fluorescent signal also cleaves non-target RNA probes conjugated with a
fluorescent dye (F) and quencher (Q) pair. Similarly, the DETECTR (DNA endonuclease-
targeted CRISPR trans reporter) method uses a crRNA-Css12a complex to recognize amplified
DNA targets. Binding of the crRNA-Cas12a complex to target DNA induces indiscriminate
cleaving of non-target FO-DNA reporters.5

The SHERLOCK technology based on Cas13 and RPA amplification was used for the detection
of SARS-CoV-2.5,14,18 This method designed a nucleic acid test strip that specifically targeted S
gene and ORFlab gene of SARS-CoV-2. It could achieve the detection of SARS-Cov-2 within 1
hour, and the sensitivity was 10 to 100 copies /μL. Except, a strategy based on test strips that
coupled Cas12 with RT-LAMP to establish a visual detection method for SARS-CoV-2 was
reported recently. As low as 10 copies/μL of extract RNA could be detected within 45 minutes
by the reported method. It is a rapid detection of COVID-19.5,14

Kumar et al.16 concluded that CRISPR-based diagnosis is accurate, point-of-care use, rapid, and
simple. This tool is cost-effective in resource poor setting. This tool is easy to use and portable
for the diagnosis of COVID-19. The CRISPR/Cas technology as DETECTR and AIOD-CRISPR
can be very helpful for large-scale screening of affected populations. These techniques can help
in routine surveillance and restricting the spread of the virus in the community.16

Enzyme-linked immunosorbet assay

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 Enzyme-linked immunosorbent assay (ELISA) is a laboratory-based test with high sensitivity
and throughput. It typically uses a multi-well plate coated with viral proteins. The analytical
sensitivity is down to picomolar (pM) ranges, and the typical assay time is two to five hours.5

Prevention

Three ways are important for preventing COVID-19 (Figure 1). These include use of vaccines
and plant extracts, such as Curcuma longa. The other one, that is important for preventing this
disease, includes cover mouth and nose in public with a mask, keep a distance from others, and
wash hands often and disinfect frequently touched surfaces at home.

Vaccines

The immune response to SARS-CoV-2 has not been completely typified. In such circumstances,
predicted computational algorithms may prove to be beneficial tools for identification of
immunogenic T-cell and B-cell epitopes that can accelerate the rational design of SARS-CoV-2
vaccine formulations. This tool is used for designing vaccines rare and emerging diseases when
immunologic data and biologic samples are limited. In addition, computer-based algorithms fail
to identify up to 20% of peptides presented by HLA molecules 6 Little safety data are available
and the efficacy in preventing severe disease are unclear. Peer-reviewed publication should
resolve these issues.15 It suggests that more data, especially long-term data, are needed to make
sure that vaccines are safe and efficacious for using on humans. Vaccines are important for
preventing COVID-19. However, human health is more important.

Vaccines for SARS-CoV-2 are aggressively being pursued. Vaccine development is typically a
lengthy process, often requiring multiple candidates before one proves to be safe and effective.
Several platforms are being used to develop candidate vaccines for Phase 1 and 2 trials. Those
that show promise are rapidly moving into Phase 3 trials. Several standard platforms, such as
inactivated vaccines, live-attenuated vaccines, and protein subunit vaccines, are being pursued.
Some novel approaches are being investigated, including DNA-based and RNA-based strategies,
replicating, and non-replicating vector strategies, with the hope of identifying a safe and
effective SARS-CoV-2 vaccine that can be used in the near future.11

There are over 120 additional vaccines in various stages of preclinical development, and the
number increases weekly. A wide variety of vaccine approaches are being used, including DNA
and RNA vaccines, live coronavirus vaccines, inactivated vaccines, subunit vaccines
(predominantly S protein), vectored vaccines (e.g., vesicular somatic virus, adenovirus, MVA,
measles virus), and peptide-based vaccines. Several vaccine candidates have completed phase 3
trials.6 These include such as Moderna Inc (Biomedical Advanced Research and Development),
Pfizer Inc (BioNTech SE), and Sinovac Research and Development (Table 2).1,6

Curcuma longa

Curcumin or diferuloylmethane with chemical formula of [1,7-bis(4-hydroxy-3-methoxyphenyl)-

1,6-heptadiene-3,5-dione] and other curcuminoids constitute the main phytochemicals of

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 Curcuma longa L.19 Curcuma longa L. belongs to the family Zingiberacea with common name
of turmeric. It is spice both for vegetarian and non-vegetarian food for preparation. It also has
digestive properties.20 It is widely available in Indonesia. Curcuma longa is a yellow chemical
compound especially on the root of the plants. Cucurmin has such as antiAlzheimer,21 anti-
ageing,21 antibacterial,19,22 anticancer,22,23,24 and antiprozoa,22 (Table 3). Curcumin is abundant in
Asian countries. It has been used worldwide. These include China, India, Indonesia, Japan,
Korea, Malaysia, Pakistan, Thailand, and the United States.30

Curcumin is available in several forms including capsules, cosmetics, energy drinks, ointments,
soaps, and tablets. The United States Food and Drug Administration (FDA) has approved
curcuminoids as “Generally Recognized As Safe” (GRAS), and good tolerability and safety
profiles have been shown by clinical trials. It is event at doses between 4,000 and 8,000
milligrams per day and at doses up to 12,000 milligrams per day of 95% concentration of three
curcuminoids: curcumin, disbemethoxycurcumin, and demethoxycurcumin.25

Rajagopal et al.7 concluded that from the docking study, the chemical constituents of turmeric
(Curcuma longa) demonstrated better arrangement at a dynamic site. The in silico structuring
strategy embraced in their investigation helped for recognizing some lead molecules and
furthermore may somewhat clarify their useful impact for further determinations like in vitro and
in vivo assessments. Results from the in silico study exhibited that many of the chemical
constituent from Curcuma longa may be useful against COVID-19 by inhibiting SARS-CoV-2
main protease enzyme. Based on in silico studies, the chemical constituents such as
cyclocurcumin and curcumin from turmeric are significantly active against COVID-19 by
inhibiting SARS-CoV-2 protease enzyme with remedial possibilities and are probably going to
be helpful after further refinement. It seems that consuming turmeric in our diet regularly may be
a useful remedy in the prevention of the coronavirus.7

Dietary administration of curcumin with dose of 150 milligrams per kilogram per day, gavage
during Ang II infusion, decreased the protein level of AT1 receptor and enhanced the expression
of AT2 receptor/ACE2 and result in the attenuation of myocardial fibrosis in a rat model of
angiotensin II infusion. These data suggest that similar events happen in the lung tissues to
prevent fibrosis. However, this hypothesis needs further studies. An oral dose of curcumin up to
8000 milligrams per day was safe, tolerable and effective in humans. A dose of 500 milligrams,
that was taken two times a day during 30 days is safe32 “A case study” in my institution
succeeded to treat gastritis (stomach inflammation) using curcumin. It was own experience. An
oral dose of curcumin up to 20 grams (about as big as a thumb), that was taken two times a day
during 5 days (or up to a week) treated the disease. Blood type of the patient was type O. Blood
pressure was normal. He was in chronic gastritis. To treat this disease, he was given turmeric
mixed with water. Clean, peel the curcumin and mash it. Then, add about 250 milliliters water (1
glass) and bring to a boil, and drink it. Until now, the patient continued to drink this twice a week
(one glass at a time) on a regular basis. This dose can also be used two times a week for
preventing dengue and covid-19. In certain condition, it can be taken three times or each day
according to need. However, these findings still need further investigations. Be careful, turmeric
is anti-hypertension (Table 3). Turmeric can cause blood pressure to drop.

Treatment

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 Use of drug(s) can help treatment of COVID-19 (Figure 1). Drug candidates are available for
treating COVID-19. These include such as Curcuma longa and remdesivir. Other drug
candidates are such as chloroquine/hydroxychloquine,7 dexamethasone,9 and
litonavir/rritonavir.33 Shanmungarajan et al.27 studied fourteen natural curcuminoids for
possibility in inhibiting SARS-CoV-2. The authors studied curcuminoids in silico properties. In
their study, the authors stated that the receptor-ligand interaction study suggested both forms of
the curcumin pharmacophore have the ability to interact with the spike glycoprotein, anchoring
the residues of ACE2. In addition, blocking these residues possibly does not facilitate its
interaction with human ACE2 receptor, and thereby viral infection can be controlled. During
docking, it was observed that curcumin keto and enol interact with TM alpha helix of the E
protein to form hydrogen and hydrophobic interaction, respectively. Thus, curcumin may be a
candidate compound for treating SARS-CoV-2. It can repair damage in lungs26 and can prevent
the development of hypertension.27. Curcuma longa can protect various organs (Table 3). It may
be as a natural defense against various diseases, including COVID-19.

The US Food and Drug Administration (FDA) approve remdesivir for treatment of COVID-19.
In patients with severe COVID-19, remdesivir reduced the time to clinical recovery. However,
there was not observed benefit of remdesivir in patients with mild or moderate COVID-19. The
number of participants in these categories was relatively small. In this study, patients were ≥ 18.
Patients received either placebo for ten days or intravenous remdesivir at a dose of 200
milligrams on day one and then 100 milligrams daily for up to 9 more days. The primary study
endpoint was time to clinically recovery. Remdesivir significantly reduced the time to recovery
compared to placebo. Ten days versus 15 days was the median time.10

Curcumin alone may treat COVID-19. It can also be used in other drugs or candidate drugs. For
example, it can be used in combination with remdesivir. Combination of these both drugs can
accelerate the cure of COVID-19. In case of schistosomiasis, Kurn et al.34 suggested that
prevention (vaccination) in combination with mass drug administration (MDA) using raziquantel
can achieve the WHO goals for eliminating schistosomiasis.34 Therefore, it suggests that the use
of Curcuma longa both for prevention and treatment can help eliminate COVID-19.

Conclusions

The SARS-CoV-2 causes COVID-19 pandemic. The COVID-19 has affected more than 61
million patients with more than 1.4 million deaths, and increasing every day. To control
COVID-19, diagnosis has an important role. Diagnosis techniques can include RT-PCR and
SHERLOCK. Drugs for this disease could be Curcuma longa and/remdesivir. Both can help
eliminate COVID-19. Curcuma longa is safe and effective. It is a good natural defense against
diseases such as COVID-19. Curcuma longa has many beneficial for health such as anti-
Alzheimer, anti-ageing, and anti-hypertension. Many countries have used turmeric for daily
needs. These countries include such as China, India, Indonesia, and the United States. Other
drugs may be such as chloroquine/hydroxychloroquine and dexamethasone. Current vaccines
may be safe; however, no long-term data are available, suggesting still needs further
investigations. Vaccines could include Moderna, Pfizer, and Sinovac products.

10

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 Funding

This study received no funding from any funding agency.

Acknowledgement

Exclusively, M. Nelwan performed research and manuscript development.

Conflict of interest

I hereby declare that I have no conflicts of interests regarding the content of this article.

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 Figures

Health people

infected people

Prevention:
Turmeric or Human with
Vaccine(s) COVID-19

Treatment:
Turmeric and/or
Remdesivir,
Chloroquine or
Hydroxychloroquine,
Litonavir/ritonavir

Health people
Dead people, if any

Figure 1. Prevention and treatment of COVID-19 using Curcuma longa, remdesivir or other
drugs such as chloroquine/hydroxychloroquine and dexamethasone.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3748111
 Tables

Table 1. Important diagnosis tools of COVID-19

Tools time references
DETECTR 30 minutes Kilic et al.5
ddPCR 60 minutes Li et al.12
Nan et al.15
Kilic et al.5
ELISA 2 to 5 hours Kilic et al.5
MinION 6 to 10 hours Nan et al.15
sequencing
RDT < 15 minutes Kilic et al.5
RT-LAMP 15 to 60 minutes Kilic et al.5
El-Azisi and
Stockhand14
Li et al.12
Nan et al.15
RT-NEAR < 15 minutes Kilic et al.5
RT-RPA 30 minutes Kilic et al.5
RT-qPCR 2 to 4 hours Kilic et al.5
STOP < 70 minutes Kilic et al.5
Kumar et al.17
DETECTR = DNA endonuclease-targeted CRISPR
transporter; dd = digital droplet; ELISA = enzyme-linked
immunoabsorbent assay; LAMP = loop-mediated
isothermal amplification; NEAR = nicking endonuclease
amplification reaction; PCR = polymerase chain
reaction;
qPCR = quantitative PCR; RPA = recombinase
polymerase
amplification; RT = reverse transcription; STOP =
SHERLOCK testing.

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 Table 2. Vaccine candidates of COVID-19
NCT number Manufacturer References
NCT04324606 University of Oxford Poland et al.6
NCT04336410 Inovio Samrat et al.1
NCT04447781 Pharmaceuticals,
International vaccine
Institute
NCT04334980 Symvivo Cororation Samrat et al.1
NCT4352608 Sinovac Research Poland et al.6
and Development
Co, Ltd
NCT04368728 BioNTech SE Poland et al.6
Pfizer Inc
NCT04400838 University of Oxford Poland et al.6
NCT04405076 Moderna Inc Poland et al.6
NCT04437875 Gamaleya Research Poland et al.6
Institute of
Epidemiology
NCT04445389 Genexine Consortium Samrat et al.1

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 Table 3. Effects of Curcuma longa
Effects References
AntiAlzheimer Valizadeh et al.21
Rajagopal et al.7
Antiaging Rajagopal et al.7
Antibacterial Marbawati and
Umiyati23
Moghadamtousi et
al.19
Gupta et al.20
Anticancer Marbawati and
Umiyati22
Kali et al.23
Anticoagulants Marbawati and
Umiyati22
Antidengue Marbawati and
Umiyati22
Antidiabetic Marbawati and
Umiyati22
Rajagopal et al.7
Shamunagarajan et
AntiEbola, al.26
hepatitis, HIV,
HSV, IAV
(influenza)
Antihypertensi Yao et al.27
Aniinflammatory Rajagopal et al.7
Antiprotozoa Marbawati and
Umiyati22
Antischistosomiasis Morais et al.29
Antivirus Marbawati and
Umiyati22
Moghadamtousi et
al.19
Cardiac repair Valizadeh et al.21
Wang et al.29
Gastroprotective Rajagopal et al.7

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 Hepatoprotective Kali et al.23
Hewlings and
On degerative eye Kalman25
condition, kidney,
pain
On lung injury Huang et al.30
injury
Potential therapy Zhu et al.31
for asthma

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