Natural products and phytochemicals as potential anti‐SARS‐CoV‐2 drugs

Abstract

The current pandemic responsible for the crippling of the health care system is caused by the novel SARS‐CoV‐2 in 2019 and leading to coronavirus disease 2019 (COVID‐19). The virus enters into humans by attachment of its Spike protein (S) to the ACE receptor present on the lung epithelial cell surface followed by cleavage of S protein by the cellular transmembrane serine protease (TMPRSS2). After entry, the SARS‐CoV‐2 RNA genome is released into the cytosol, where it highjacks host replication machinery for viral replication, assemblage, as well as the release of new viral particles. The major drug targets that have been identified for SARS‐CoV‐2 through host‐virus interaction studies include 3CLpro, PLpro, RNA‐dependent RNA polymerase, and S proteins. Several reports of natural compounds along with synthetic products have displayed promising results and some of them are Tripterygium wilfordii, Pudilan Xiaoyan Oral Liquid, Saponin derivates, Artemisia annua, Glycyrrhiza glabra L., Jinhua Qinggan granules, Xuebijing, and Propolis. This review attempts to disclose the natural products identified as anti‐SARS‐CoV‐2 based on in silico prediction and the effect of a variety of phytochemicals either alone and/or in combination with conventional treatments along with their possible molecular mechanisms involved for both prevention and treatment of the SARS‐CoV‐2 disease.

Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics Simulations

“…Many plant-derived molecules have been studied using computational approaches (docking and dynamic studies) targeting SARS-CoV-2 key enzymes including papainlike proteases (PLpro), 3C-like protease (Mpro) and NSP15 proteins. Several molecules have been reported to bind to active site of these three SARS-CoV-2 proteins with high binding affinity [41][42][43][44][45][46][47][48]. In silico studies have shown that various natural products have strong binding affinity to the non-structural proteins of SARS-CoV-2 virus (PLpro, Mpro and RdRp), and structural proteins such as spike (S) protein [43,49].…”

Mast cells: Therapeutic targets for COVID‐19 and beyond

“…44 The COVID-19 pandemic presents an unprecedented challenge to the healthcare system globally and causes a huge stress on the economy worldwide. 72,74 SARS-CoV-2 has glycoprotein spikes projecting from its envelope, giving it a crown-like structure. 71,74 Four structural proteins, spike glycoprotein (S), small envelope glycoprotein (E), membrane glycoprotein (M) and nucleocapsid protein (N) and 16 non-structural proteins have been identified.…”

“…Coronaviruses are single positive‐strand, enveloped ribonucleic acid viruses. 71 , 72 Within the last 20 years, there have been three highly pathogenic, zoonotic diseases caused by coronaviruses, with Severe Acute Respiratory Syndrome (SARS‐CoV‐1) first being detected in China in 2002 and then Middle East Respiratory Syndrome coronavirus (MERS‐ CoV) in Saudi Arabia in 2012, both caused outbreaks and spread globally. 71 , 73 , 74 There were more than 8000 SARS‐CoV‐1 cases with about 10% mortality rate whereas MERS‐CoV had about 2500 cases and an almost 40% mortality rate.…”

“…44 The COVID‐19 pandemic presents an unprecedented challenge to the healthcare system globally and causes a huge stress on the economy worldwide. 72 , 74 …”

Phytochemicals: Potential Lead Compounds for COVID-19 Therapeutics

“…In spite of the fact that numerous drugs do exist that have clinically proven antiviral properties (Indari et al, 2021) and several drugs that show a limited potential to alleviate COVID-19 symptoms (Lam et al, 2020;Raju et al, 2021), none of them have proven to work efficiently to reduce COVID-19 associated mortality. Nevertheless, several in vitro studies have demonstrated the potential of several phytochemicals to inhibit COVID-19 infectious cycle in humans at various stages (Alam et al, 2021;Behl et al, 2021;Marmitt et al, 2021;Merarchi et al, 2021). These phytochemicals have been demonstrated to inhibit viral entry, viral replication, or viral release -in addition to attenuating the host pathological responses (Figure 2).…”