5/29/21

1st IC MTech
International Conference on Medical Technology

;#$(#"1<*('3*=)#"'#&(-*>"2"($.?*)'*@"(-#?*
A$"(*$"-(#"3*#)*B('3"%&.**4)5&3678*

!"#"$%&'(#&)'*)+*,)-"./-($*
0($1"#2*+)$*!&(1')2&2*('3*
0$"(#%"'#*)+*4)5&3678***********
9&'*2&-&.):**

PROF. DR MOHD NAZIL SALLEH,

PhD, CSci, FIBMS, FMIMLS

29 May 2021| Lombok Indonesia

01.
Introduction
Chronology of Covid-19
Structure and Mutations

1
 5/29/21

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

causes COVID-19

SARS-CoV-2 is a new virus. The first cases were identified in people with pneumonia in Wuhan, China, in
late December 2019. It probably started in animals but is now spreading between people.

The World Health Organization (WHO) declared the situation a pandemic on 11 March 2020 signifying

• Widespread human-to-human transmission

• Large number of affected countries

Cumulative number of cases diagnosed with COVID-19 in the world was more than 153 million, whereas
more than 3 million cases died

Although there is a lot we don’t know yet about this new virus, we can still prevent the disease.

2
 5/29/21

3
 5/29/21

SARS-CoV-2 variants are defined as viruses accumulating mutations, including single nucleotide
polymorphisms (SNPs), that confer them with a selection advantage such as higher infectivity within the host
and transmissibility between hosts [3].
Variants of concern are defined as viruses that have acquired antigenic changes altering the immune
response and/or drug efficacy. Genome sequencing allows visualization of the virus's ongoing evolution.
While mutations have been reported throughout the SARS-CoV-2 genome, the most concerning ones have
occurred in the Spike (S) encoding gene. ADVANCES IN CELL AND GENE THERAPY, Volume: 4, Issue: 2, (2021)

ADVANCES IN CELL AND GENE THERAPY, Volume: 4, Issue: 2, First published: 12 February 2021, DOI: (10.1002/acg2.107)

SARS-CoV-2 variants are defined as viruses accumulating

mutations, including single nucleotide polymorphisms (SNPs),
that confer them with a selection advantage such as higher
infectivity within the host and transmissibility between
hosts [3].
Variants of concern are defined as viruses that have
acquired antigenic changes altering the immune response
and/or drug efficacy. Genome sequencing allows visualization
of the virus's ongoing evolution. While mutations have been
reported throughout the SARS-CoV-2 genome, the most
concerning ones have occurred in the Spike (S) encoding
gene.

4
 5/29/21

02.
Pathophysiology of Covid 19
In silico screening of potent bioactive
compounds

• The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome
coronavirus-2 (SARS-CoV-2),
• has spread globally since the first fatal cases were reported in Wuhan, China, and the World Health
Organization declared it a pandemic on March 11, 2020 [WHO].
• Epidemiological and clinical characteristics of COVID-19 findings patients suffered from severe
pneumonia, which can progress to acute respiratory distress syndrome (ARDS), multiple organ failure,
and death, especially in older patients with underlying diseases such as diabetes and cardiovascular
disorders [Deng and Peng 2020; Park et al 2020; Ciotti et al 2020]
• The pathophysiological mechanisms leading to decreased lung injury specifically, decreased expression
of proteins, including angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2
(TMPRSS2) in the airway epithelium in.
• The immune system differences may include a relative preponderance of CD4+ T cells, decreased
neutrophil infiltration, decreased production of proinflammatory cytokines, and increased production of
immunomodulatory cytokines

10

5
 5/29/21

Pathophysiological of Covid 19 in human system

11

Traditional workflow of structure-based drug design (SBDD) and ligand-based drug design (LBDD)

12

6
 5/29/21

Structure based Drug Determination Ligand Based Drug Design

• Relies on knowledge of other
• Protein Structure Determination Molecules that bind to the biological
• Docking Target of interest
• Binding Free Energy • Derive from pharmacophore model
• Flexibility of Protein ligand Complex • Product that derive from correlation
• De novo evolution Calculated properties - QSAR
• New analogues predicated from
QSAR

13

• This virus caused of “cytokine storms” (Huang et al., 2020; Shen et al., 2020; Ye et al.,
2020). increased expression of inflammatory cytokines (IL-6, IL-10, IL-2, and IFN-g).
• Confirmed studied, that a large number of patients with severe COVID-19 are likely to
ARDS whereby excess production of pro-inflammatory cytokines results in ARDS
aggravation (Howell and Davis, 2018). Therefore, there a need to search for therapies to
reduce hyper-inflammation andimprove prognosis in severe COVID-19 patients.
• .

14

7
 5/29/21

honeybee products have been proposed as a potential compatible antiseptic to help protect against the
COVID-19 based on biocidal effect of hydrogen peroxide and other phytochemicals existing in bee products
(Al Naggar et al. 2020)

These phenolic compounds and terpenes found in honeybee products were documented to possess variable
medicinal effects including wound healing, antioxidant, antimicrobial, antiviral, anti-inflammatory,
cardioprotective, and neuroprotective activities (Küçük et al. 2007; Mohamed et al. 2009; Al Naggar et
al. 2016; Pasupuleti et al. 2017; Jibril et al. 2019; El-Seedi et al. 2020; Al Naggar et al. 2020; Al Naggar et
al. 2021)

Huangqi (Radix Astragali Mongolici), it is the dried root of the leguminous plants Astragalus mongholicus. It
has been widely used in ischemic cardio-cerebrovascular disease, viral hepatitis, kidney disease, and skin
diseases for the nourishment of Qi and blood (Li et al., 2017; Gong et al., 2018). More than 40 active
constituents of astragalus root have been identified, with Astragaloside IV (PubChem, CID13943297) being
the major active compound.

15

16

8
 5/29/21

17

18

9
 5/29/21

19

03.
Conclusions

20

10
 5/29/21

UsingComputer-aided drug design (CADD) methodologies There are two main methods used for in
slico drug discovery: ligand-based drug discovery (LBDD) and structure-based drug discovery
(SBDD) the pharmacological mechanism of Astragaloside IV on COVID-19 is investigated using
network pharmacology and bioinformatics analysis. Astragaloside IV is shown to be a potential drug
for alleviating hyperinflammation in COVID-19 by inhibiting the Influenza A pathway, NOD-like
receptor signaling pathway. Therefore, we believe that Astragaloside IV is likely to be beneficial in
treating severe COVID-19 patients

21

THANKS! for your attention

!)*<)/*?(5"*('<*C/"2#&)'2D

=$)+E*!$E*,)?3 F(G&- ;(--"?

3$%)?3'(G&-HB&.)%2E"3/E%<
IJK78*LLJ*MNOJ
=P4Q,;*P'#"$'(#&)'(-*R'&5"$2&#<*4)--"1"
S(-('*O7T7KA*0(%('*U(#/*,/3(V*U(#/*4(5"2V*
JM7KK*W/(-(*X/%B/$E*,(-(<2&(

22

11