In silico Investigation of Saponins and Tannins as Potential Inhibitors of SARS-CoV-2 main Protease (Mpro)

Abstract

It is no longer news that a novel strain of coronavirus named SARS-CoV-2 is ravaging the health sector worldwide, several attempts have been made to curtail this pandemic via repurposing of old drugs but at the present, available drugs are not adequately effective. Over the year, plant phytochemicals are increasingly becoming an alternative source of an antimicrobial agent with a novel mechanism of action and limited side effects compared to synthetic drugs. Isolated saponins and tannins were evaluated for antiviral activity against SARS-CoV-2 Mpro via Molecular Docking and it was observed that a handsome number of the phytochemicals had binding affinity much better than Remdesivir, Dexamethasone, and N3 inhibitor which were used as the standard in this study. Further Investigation of drug-likeness, ADMET profile, and bioactivity of these phytochemicals revealed that binding affinity alone is not enough in the drug discovery process and that 4 hit compounds were identified as potential inhibitors of SARS-CoV-2Mpro. This preliminary study furnishes Ellagic acid, Arjunic acid, Theasapogenol B, and Euscaphic acid as potential inhibitors of SARS-CoV-2 Mpro with better pharmacokinetics and bioavailability compared to Remdesivir which is currently used compassionately.

Chemical Constituents of the Bark of Zanthoxylum gilletii (Rutaceae) and Their In Vitro Antiplasmodial and Molecular Docking Studies

“…Cytochrome P450 inhibitors are responsible for the biotransformation of a drug; a potential drug should not alter their kinetics [34]. Te results show that although compounds 1 (2/5), 2 (3/5), 3 (4/5), and 5 (3/5) violated the minimum inhibition allowed as reported by Falade et al [19], compounds 8 (0/5), 9 (0/5), 12 (1/5), and 13 (0/5) show an improved value of less inhibition compared to chloroquine (2/5).…”

“…Te receptor was obtained from the (RCSB) database (https://www.rcsb.org/pdb). Te resolution of receptor 5TBO (2.15 Å) approximately lies about the 2.0 Å recommended resolution for a receptor of good quality [19]. Water molecules around the crystal structure and other associated inhibitors were removed from the downloaded protease to avoid undesired interferences and unwanted molecular interactions.…”

“…In modern computer-assisted drug design (CADD), the study of a potent drug is not complete without the activity study of the drug which is deducible from the compound's inhibition constant. A potent compound is expected to have inhibition constant values ranging between 0.01 and 1 μM for a potent drug; therefore, this parameter alone is enough to screen compounds in the drug discovery journey [19].…”

Lancemaside A from Codonopsis lanceolata is a broad-spectrum antiviral agent against SARS-CoV-2 and variants of concern

“…Saponins including triterpenoid saponins derived from various medicinal plants have also been investigated for their therapeutic potential against SARS-CoV-2 (Ebob, Babiaka & Ntie-Kang, 2021). But, most are based on in silico studies (Diniz, Perez-Castillo, Elshabrawy, Filho & de Sousa, 2021;Falade, Adelusi, Adedotun, Abdul-Hammed, Lawal & Agboluaje, 2021;Sinha et al, 2021;Yang et al, 2020) and it is only recently that their inhibitory activities have been demonstrated using pseudotyped or authentic SARS-CoV-2. Licoricesaponin A3, a triterpenoid saponin isolated from licorice, was reported to inhibit SARS-CoV-2 by targeting the NSP7, a core component of RdRp (Yi et al, 2022).…”

Individual and Synergistic Potential of Bioactive Compounds from Chrysopogon Zizanioides Against Main-Protease of SARSCov-2 using Computational Approach

“…There has been no report on the simultaneous synergistic effect of Chrysopogon zizanioides against M pro 30 . The top-ranked Apart from essential oils, the antiviral potentials of various flavonoid polyphenols, alkaloids, saponins, tannins, terpenoids, etc., were studied [35][36][37][38][39] . No compounds possessed toxicity and carcinogenic properties predicted using SwissADME and admetSAR webservers (Table 4), thus are safe for consumption without any side effects.…”