ADMET profile and virtual screening of plant and microbial natural metabolites as SARS-CoV-2 S1 glycoprotein receptor binding domain and main protease inhibitors

Abstract

In an attempt to search for selective inhibitors against the SARS-CoV-2 which caused devastating of lives and livelihoods across the globe, 415 natural metabolites isolated from several plants, fungi and bacteria, belonging to different classes, were investigated. The drug metabolism and safety profiles were computed in silico and the results showed seven compounds namely fusaric acid, jasmonic acid, jasmonic acid methyl ester, putaminoxin, putaminoxin B and D, and stagonolide K were predicted to having considerable absorption, metabolism, distribution and excretion parameters (ADME) and safety indices. Molecular docking against the receptor binding domain (RBD) of spike glycoprotein (S1) and the main protease (M pro ) exposed the compounds having better binding affinity to main protease as compared to the S1 receptor binding domain. The docking results were compared to an antiviral drug penciclovir reportedly of clinical significance in treating the SARS-CoV-2 infected patients. The results demonstrated the test compounds jasmonic acid, putaminoxins B and D bound to the HIS-CYS catalytic dyad as well as to other residues within the M Pro active site with much greater affinity than penciclovir. The findings of the study suggest that these compounds could be explored as potential SARS-CoV-2 inhibitors, and could further be combined with the experimental investigations to develop effective therapeutics to deal with the present pandemic.

Chemical signals driving bacterial–fungal interactions

“…Moreover, the ongoing pandemic of COVID‐19 has changed the entire perspective of infectious diseases where one potent microbe can affect the entire world regardless of the constraints of geographical boundaries. This current situation further underscores the necessity for novel and more effective drugs in order to establish a defence line against COVID‐19 with microbial natural products already being screened for potential therapeutic use (Brüssow, 2020; Zahran et al ., 2020, Padhi et al ., 2021).…”

A Multifunctional Peptide From Bacillus Fermented Soybean for Effective Inhibition of SARS-CoV-2 S1 Receptor Binding Domain and Modulation of Toll Like Receptor 4: A Molecular Docking Study

“…In view of this, scores of studies have investigated the possible antiviral effects of several natural metabolites, including organic compounds and peptides, and drugs against SARS-CoV-2 protein targets (Luo et al, 2020;Vincent et al, 2020;Padhi et al, 2021;Yu et al, 2021). Fermented soy products have been recommended as a possible therapy for SARS-CoV-2 infected patients in Japan.…”

“…Therefore, researchers worldwide are racing to find a possible intervention using functional foods and natural compounds as pharmaceuticals. In view of this, scores of studies have investigated the possible antiviral effects of several natural metabolites, including organic compounds and peptides, and drugs against SARS-CoV-2 protein targets ( Luo et al, 2020 ; Vincent et al, 2020 ; Padhi et al, 2021 ; Yu et al, 2021 ).…”

A Potential Peptide From Soy Cheese Produced Using Lactobacillus delbrueckii WS4 for Effective Inhibition of SARS-CoV-2 Main Protease and S1 Glycoprotein

“…Thus, residues in the substrate-binding site of the two enzymes have very high similarity (RMSD = 0.99 Å) (Macchiagodena et al, 2020). Knowledge of conserved RBM location in S1 glycoprotein and high 3CL pro sequence homology and substrate conservation between β-coronaviruses can be explored to develop broad-spectrum inhibitors against viral infections to prevent the damage caused by the emergence of future SARS-like respiratory illnesses (Padhi et al, 2020). KFVPKQPNMIL showed interactions with RBD of SARS-CoV, including conventional hydrogen bond interactions with critical residues responsible for receptor attachment.…”

“…The causative organism of this outbreak is a novel viral entity belonging to the genera of β-coronavirus, which was eventually identified by the International Committee on Taxonomy of Viruses (ICTV) as Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. Researchers are focusing on the development of vaccines and bioactive metabolites from natural sources as therapeutics (Corbett et al, 2020;Izda et al, 2020;Padhi et al, 2020). Among vaccines, two leading mRNA-based SARS CoV-2 vaccine candidates, mRNA-1273, and BNT162b1-b2 have demonstrated a robust anti-SARS-CoV-2 neutralizing antibody response in clinical trials (Anderson et al, 2020;Mulligan et al, 2020).…”