Comparative docking studies of drugs and phytocompounds for emerging variants of SARS-CoV-2.

In the last three years, COVID-19 has impacted the world with back-to-back waves leading to devastating consequences. SARS-CoV-2, the causative agent of COVID-19, was first detected in 2019 and since then has spread to 228 countries. Even though the primary focus of research groups was diverted to fight against COVID-19, yet no dedicated drug has been developed to combat the emergent life-threatening medical conditions. In this study, 35 phytocompounds and 43 drugs were investigated for comparative docking analysis. Molecular docking and virtual screening were performed against SARS-CoV-2 spike glycoprotein of 13 variants using AutoDock Vina tool 1.5.6 and Discovery Studio, respectively, to identify the most efficient drugs. Selection of the most suitable compounds with the best binding affinity was done after screening for toxicity, ADME (absorption, distribution, metabolism and excretion) properties and drug-likeliness. The potential candidates were discovered to be Liquiritin (binding affinities ranging between -7.0 and -8.1 kcal/mol for the 13 variants) and Apigenin (binding affinities ranging between -6.8 and -7.3 kcal/mol for the 13 variants) based on their toxicity and consistent binding affinity with the Spike protein of all variants. The stability of the protein-ligand complex was determined using Molecular dynamics (MD) simulation of Apigenin with the Delta plus variant of SARS-CoV-2. Furthermore, Liquiritin and Apigenin were also found to be less toxic than the presently used drugs and showed promising results based on in silico studies, though, confirmation using in vitro studies is required. This in-depth comparative investigation suggests potential drug candidates to fight against SARS-CoV-2 variants. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03450-6.

Comparative docking studies of drugs and phytocompounds for emerging variants of SARS-CoV-2

In the last three years, COVID-19 has impacted the world with back-to-back waves leading to devastating consequences. SARS-CoV-2, the causative agent of COVID-19, was first detected in 2019 and since then has spread to 228 countries. Even though the primary focus of research groups was diverted to fight against COVID-19, yet no dedicated drug has been developed to combat the emergent life-threatening medical conditions. In this study, 35 phytocompounds and 43 drugs were investigated for comparative docking analysis. Molecular docking and virtual screening were performed against SARS-CoV-2 spike glycoprotein of 13 variants using AutoDock Vina tool 1.5.6 and Discovery Studio, respectively, to identify the most efficient drugs. Selection of the most suitable compounds with the best binding affinity was done after screening for toxicity, ADME (absorption, distribution, metabolism and excretion) properties and drug-likeliness. The potential candidates were discovered to be Liquiritin (binding affinities ranging between −7.0 and −8.1 kcal/mol for the 13 variants) and Apigenin (binding affinities ranging between −6.8 and −7.3 kcal/mol for the 13 variants) based on their toxicity and consistent binding affinity with the Spike protein of all variants. The stability of the protein–ligand complex was determined using Molecular dynamics (MD) simulation of Apigenin with the Delta plus variant of SARS-CoV-2. Furthermore, Liquiritin and Apigenin were also found to be less toxic than the presently used drugs and showed promising results based on in silico studies, though, confirmation using in vitro studies is required. This in-depth comparative investigation suggests potential drug candidates to fight against SARS-CoV-2 variants. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03450-6.

Changing Dynamics of SARS-CoV-2: A Global Challenge

Since November 2019, SARS-CoV-2 has been a matter of global concern due to its rapid spread, the millions of deaths it caused, and repeated waves of infections. One after another, many variants of this novel virus have come into existence due to its constant mutability, specifically in the spike glycoprotein region. The tally for variants of concern (VOCs), which already include Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2), has increased to five with the latest appearance of Omicron (B.1.1.529). In our study, we examine the effect of the transmissibility and infectious potential of the virus due to various mutations of SARS-CoV-2, especially in the receptor-binding domain (RBD). We discuss the role of genome sequencing in tracing all the mutations and the importance of the R value (reproductive number) to understand the virus spread. We also review the effectiveness of the available vaccines on the variants of concern, as the rapid spread of the newly emergent Omicron variant has raised doubts about the usefulness of the current vaccines. The use of a mixed vaccination strategy has proved to be effective, yet the newer variants, such as Omicron, demand booster doses for the population. Multivalent immunogens could be considered as the plausible solution for conferring protection against potential new mutants of the virus in the future.