Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein

Abstract

In this in silico study, we conducted an in-depth exploration of the potential of natural products and antihypertensive molecules that could serve as inhibitors targeting the key proteins of the SARS-CoV-2 virus: the main protease (Mpro) and the spike (S) protein. By utilizing Induced Fit Docking (IFD), we assessed the binding affinities of the molecules under study to these crucial viral components. To further comprehend the stability and molecular interactions of the “protein-ligand” complexes that derived from docking studies, we performed molecular dynamics (MD) simulations, shedding light on the molecular basis of potential drug candidates for COVID-19 treatment. Moreover, we employed Molecular Mechanics Generalized Born Surface Area (MM-GBSA) calculations on all “protein-ligand” complexes, underscoring the robust binding capabilities of rosmarinic acid, curcumin, and quercetin against Mpro, and salvianolic acid b, rosmarinic acid, and quercetin toward the S protein. Furthermore, in order to expand our search for potent inhibitors, we conducted a structure similarity analysis, using the Enalos Suite, based on the molecules that indicated the most favored results in the in silico studies. The Enalos Suite generated 115 structurally similar compounds to salvianolic acid, rosmarinic acid, and quercetin. These compounds underwent IFD calculations, leading to the identification of two salvianolic acid analogues that exhibited strong binding to all the examined binding sites in both proteins, showcasing their potential as multi-target inhibitors. These findings introduce exciting possibilities for the development of novel therapeutic agents aiming to effectively disrupt the SARS-CoV-2 virus lifecycle.

Exploration of the in vitro Antiviral Effects and the Active Components of Changyanning Tablets Against Enterovirus 71

“…Besides the anti-EV71 activity, rosmarinic acid was reported to be efficient against a variety of other viruses, including severe acute respiratory syndrome coronavirus, herpes simplex virus, dengue virus, influenza A virus, and hepatitis B virus. 36,[47][48][49][50] Therefore, rosmarinic acid might be a broad-spectrum antiviral compound. Another component we are concerned with is rutin, which was identified from both AEMC and AELLF by HPLC-Q-TOF-MS/MS, and was also demonstrated to bind tightly with two of the three core targets (AKT1 and ALB) by molecular docking.…”

Quercetin: A Potential Polydynamic Drug

“…Quercetin has been found to be able to interfere with SARS-CoV-2 and reduce the inflammation provoked by COVID-19 (Scheme 2). Also, blood tests have indicated that quercetin can reduce the time during which the molecular test appears positive by reducing the viral charge [33].…”

Triple Generative Self-Supervised Learning Method for Molecular Property Prediction

“…Drug development is a time-consuming and costly process. In order to improve the success rate and reduce the time and costs, computer-aided drug design (CADD) [1,2] methods such as virtual screening and molecular docking have been introduced to provide guidance for the entire process. Despite their success in drug discovery [3,4], many traditional CADD methods based on molecular simulation techniques suffer from high computational costs and long running times, which limit their large-scale application in the pharmaceutical industry.…”