Review Article OPEN ACCESS | Freely available online

Antiviral compounds from marine bivalves for evaluation against

SARS-CoV-2
Chee Kong Yap*
Department of Biology, Faculty of Science, Universiti Putra Malaysia,43400 UPM, Serdang, Selangor, Malaysia.

Abstract: A novel corona virus (SARS-CoV-2) outbreak is claiming thousands of lives worldwide. As of April 10, 2020, the number of
laboratory-confirmed cases of SARS-CoV-2 infected has reached over 1.7 million (1,725,126) with over 0.1 million (104,878) recorded
deaths. This pandemic has ushered an urgent need for identifying drugs which can inhibit the survival of SARS -CoV-2. On one hand,
researchers from across globe are searching for various sources of potential antiviral compounds. On the other hand, high diversity, ecological
adaptation, defensive system against wide range of viruses makes marine bivalves as a great source of antiviral compounds. Ocean
environment has provided a rich diversity of compounds from structural classes including alkaloids, terpenoids, steroids, polysaccharides, and
peptides etc., many of which have shown potential activities against bacterial, fungal, parasitic and viral diseases. In this scenario, potential
antiviral compounds from marine bivalves, worth evaluating against SARS-CoV-2 have been briefly summarized in this present review.

Keywords: Antiviral compounds; marine bivalves; antiviral potency; SARS-CoV-2; novel corona virus.

Citation: Chee Kong Yap (2020) Antiviral compounds from marine bivalves for evaluation against SARS-CoV-2, Journal of PeerScientist
2(2): e1000015.

Received: April 01, 2020; Accepted: April 21, 2020; Published: April 22, 2020.

Copyright: © 2020 Chee Kong Yap. This is an open-access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Competing Interests: The author have declared that no competing interests exist.

* E-mail: yapckong@hotmail.com | Phone: + 603-9769 6616.

I. INTRODUCTION
novel corona virus (nCoV) outbreak in late 2019 at
A Wuhan, China is claiming thousands of lives across
globe leaving humans in a predicament situation of
novel corona virus disease (COVID-19) pandemic [1]. As
of April 10, 2020, the number of laboratory-confirmed
cases of SARS-CoV-2 infected has reached over 1.7
million (1,725,126) with over 0.1 million (104,878)
recorded deaths [2]. The incremental numbers for both
total cases and total deaths signifies that the coronavirus is
infecting humans exponentially. Present identified novel
corona virus belongs to same family of recent Severe
Acute Respiratory Syndrome (SARS) and Middle East
Respiratory Syndrome (MERS) outbreaks [3-4]. Zhang et
al. 2002 showed that the outbreaks of the Severe Acute
Respiratory Syndrome (SARS) in many regions of Asia
were well described by the logistic model, and the control
measures implemented by governments are effective [5].
Christian et al. 2014 reported that the number of patients
diagnosed positive with Middle East Respiratory
Syndrome (MERS) are with known travel history between
cities in King Fahd Hospital and all other hospitals,
between March 26 until April 28, 2014 [6]. The above two
studies shows the peak of coronavirus COVID-19 shall be
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reaching a plateau and this level-off pattern would
indicate the fall of the pandemic overall cases.
Presumably, any viral outbreak will eventually become
less contagious and harmful, and less of the public health
concern. Only the discovery or repurposing of potential
antiviral drugs (ADs) can be a good answer if not the best
to cure and save the infected patients’ lives at present, and
to control this viral pandemic COVID-19 spread.
Oceans hold exclusive supplies that can offer a wide
spectrum of natural products, principally from
invertebrates such as bivalves. As infectious diseases
change and grow endurance to existing pharmaceuticals,
the marine environment can provide an innovative
protection against bacterial and viral diseases [7].
Limitations in antiviral treatments and the occurrence of
novel pathogenic viruses have added to a mounting
requirement for novel and applicable chemotherapeutic
agents to cure viral diseases. Researches on the chemical
structures and Antiviral Compounds (ACs) [8] of
uncommon metabolic products of aquatic life have
proven that marine organisms can provide excellent
outlooks in the hunt for ADs [9]. Owing to the fact that
bivalves are in scarcity of a distinct adaptive immune
system, they must utilize their inborn immune system as a
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Figure 01: 2D structures of murexine, tyrindoleninone; 6-bromoisatin, 6,6’-dibromoindirubin and 6,6’-dibromoindigo compounds.
protection against viral infections [10-11]. Besides the
corporal obstacles of skin, shell, and epithelium, the
bivalves’ inborn immunity is also amplified by the
occurrence of numerous antimicrobial chemical agents
[12]. Biological diversity and ecological adaptations of
bivalves hint at a potential source of novel ACs for future
AD discovery. In addition, ACs are a vital part of
bivalves’ defences against viruses with varied
mechanisms of action against a wide array of viruses,
including human pathogens [13]. In this scenario, this
review aims at presenting potential antiviral compounds
from marine bivalves, worth evaluating against SARS-
CoV-2.
Figure 02: 2D structure of mytilin compound from Mytilus
galloprovincialis.
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Antiviral compounds from marine bivalves against SARS-CoV-2
Tincu, J. A., and Taylor, S. W 2004 observed
antimicrobial agents from marine bivalves can counteract
the invasions of pathogenic microbes effectively [14].
Olicard, C et.al 2005 [15] and Carriel‐Gomes et.al. 2006
[16] demonstrated antiviral activity in hemolymph from
oysters, Crassostrea gigas and C. rhizophorae. Bilal
Muhammad Khan and Yang Liu, 2019 summarized that
secondary metabolites isolated from bivalves including
mussel Mytilus galloprovincialis, mussel Crenomytilus
grayanus, clam Mercenaria mercenaria, clam Ruditapes
philippinarum, cockle Cerastoderma edule, clam
Myaarenaria, oyster C. gigas, oyster C. virginica, and
oyster Ostrea edulis have been investigated as having AP
against many human related viruses [17]. Still, there are
about 100,000 species of mollusks that remain unverified
for potential AP [13]. Kirsten Benkendorff 2009 reported
murexine, tyrindoleninone; 6-bromoisatin, 6,6’-
dibromoindirubin and 6,6’-dibromoindigo compounds as
some of the important drug like compounds from
mollusks (figure 01) [18]. In recent review by Odeleye et
al. 2019, summarized main health benefits of molluscan
extracts include anti-cancer, antioxidant, and anti-
infectious disease activities [19]. Chatterji et al. 2002
reported that the extracts from economically important
estuarine clam Meretrix casta, mussel P. viridis, mud
clam Polymesoda erosa, oyster C. madrasensis, giant
oyster C. gryphoides, and black clam Villorita cyprinoide
were found to reduce the infection of influenza virus
type-A and B to a great extent [20].
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A comprehensive review by Dang et al. 2015

summarized most characterized extracts from bivalve
species with in vitro antiviral activity. Mytilin (figure 02)
and Defensin (figure 03) from Mytilus galloprovincialis
showed direct inhibition of viral attachment and
transcription process. Defensins are cysteine rich 18-45
amino acid length peptides produced by innate immune
system and found highly active against a variety of
bacteria, fungi, enveloped and non-enveloped viruses
[13]. On the other hand, Tachyplesin I & II (figure 04) are
another set of isopeptides isolated from hemocytes of
horseshoe crab (Tachypleus tridentatus and Limulus
polyphemus) were shown to directly inactivating several
viruses including Vesicular stomatitis virus (VSV) and
Influenza (H1N1) virus [21].

Figure 04: 2D structures of Tachyplesin I & II compounds from

Tachypleus tridentatus and Limulus polyphemus.

Premalata Pati et.al, 2014 summarized unique

Figure 03: 2D structure of Defensin compound from Mytilus
galloprovinciali.s.
secondary metabolites with demonstrated anti-microbial
activies. Dolastatin 10 & 15, Kahalaide F, Keenamide A
(figure 05), Turbostatin 1, Spisulosine-ES-285,
Ulapualide-A, and Ziconotide (figure 06) are some of the
biologically active extracted, identified and isolated from
marine molluscs [22].

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Figure 05: 2D structures of Dolastatin 10 & 15, Kahalaide F and Keenamide A compounds.

Maria Jose Abad Martinez et.al, 2008 reviewed alkaloids, Alpha-galactosylceramide and clavulone
literature and summarized compounds from marine against Vesicular Stomatitis Virus (VSV) (figure 07) [7].
sources which are active against Human
Muhammed Zafar Iqbal and Khan 2016 reported
Immunodeficiency Virus (HIV) are Avarol, avarone,
a novel DNAse like compound that can inhibit viral
lamellarins, dragmacidin F, toxiusol; Herpes Simplex
propagation from the green-lipped mussel Perna viridis.
Virus (HSV) are 4a-acetyldictyodial, pseudopterosins,
They explored DNAse like bioactivity for natural non-
helioporins, 8-hydroxymanzamine A, halovirs;
proteinacious compound(s) extracted from P. viridis.
Cytomegalovirus (CMV) are Sulfolipids, plastoquinones,
These results indicated the prospect of a source of
pseudopterosin P and Influenza (H1N1) virus are
potential AD against DNA Group I viruses. Muhammed
Nostoflan and strongylin A; Human T- cell leukemia
Zafar Iqbal and Khan speculated that the marine mussels
virus , type 1 (HTLV-1) are Fistularin 3, 11-ketofistularin
have evolved some mechanisms against viral infections
3, kelletinin A; murine coronavirus is Halitunal; Hepatitis
which need further studies [22].
B (HBV) are neofolitispates, pentacyclic guanidine

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Figure 06: 2D structures of Turbostatin 1, Spisulosine-ES-285, Ulapualide-A, and Ziconotide compounds.

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Figure 07: 2D structures of Dolastatin 10 & 15, Kahalaide F, Keenamide A, Turbostatin 1, Spisulosine-ES-285, Ulapualide-A, and Ziconotide
compounds.
II. CONCLUSION
In conclusion, all the above literature indicates that
various marine sources, especially marine bivalves holds
rich diversity of compounds from structural classes
including alkaloids, terpenoids, steroids, polysaccharides,
and peptides etc., with potential antiviral potency which
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Antiviral compounds from marine bivalves against SARS-CoV-2
can be used for further studies towards converting them
into antiviral drugs. Owing to the fact that bivalves are
totally depended on their inborn immune system to
protect themselves against viral infections, they are bound
to develop a wide range of compounds which are hard to
find elsewhere. Taking these compounds as start point,
potential target specific drug like compounds can be
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designed to tackle viral infections, including present 20. Chatterji, A., Ansari, Z.A., Ingole, B.S., Bichurina, M.A.,
Sovetova, M., and Boikov, Y.A. “Indian marine bivalves: Potential
SARS-CoV-2 infections. source of antiviral drugs.” Curr. Sci., 8210 (2002): 1279-1282.
21. Murakami, Tsukasa, et al. "Direct virus inactivation of tachyplesin
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