ABSTRACT
Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as reviewed through molecular docking and sequent molecular dynamics (MD) simulations against this condition. The crystal structures of ACE2 receptors of SARS-CoV-2 and SARS-CoV, applied in docking analysis, were taken from the Protein Data Bank (PDB). The receptors were then prepared using the Molecular Operating Environment (MOE), as a drug-discovery software platform for docking. Supplements such as quercetin and beta glucan (ß-glucan) were the top docked compounds to ACE2 receptor though they strongly interacted with CoV target protein. The study data showed that immune responses to immunonutrient-based sports compounds (viz. quercetin and ß-glucan) in Coronavirus disease 2019 (COVID-19) were essential in mounting successful immune responses by athletes. While awaiting the development of an effective vaccine, there is a need to focus on immunonutrient-based sports supplements as preventive and therapeutic options that can be implemented in a safe and quick manner to bolster immune responses in athletes.Communicated by Ramaswamy H. Sarma.
ABSTRACT
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic COVID-19 disease that affects human respiratory function. Despite the scientific progression made in the development of the vaccine, there is an urgent need for the discovery of antiviral drugs for better performance at different stages of SARS-CoV-2 reproduction. The main protease (Mpro or 3CLpro) plays a pivotal role in the life cycle of the virus, making it an attractive target for the development of antiviral agents effective against the new strains of coronaviruses (CoVs). In this study, a series of apigenin-based natural biflavonoid derivatives as potential inhibitors of coronaviruses 3CLpro was investigated by in silico approaches. For this purpose, the molecular docking was performed to analyze the interaction of the natural biflavonoids with SARS-Cov-2 main protease and for further investigation, docking to the 3CLpro of SARS-CoV and MERS-CoV. Based on docking scores and comparison with the reference inhibitors (ritonavir and lopinavir), more than half of the biflavonoids had strong interactions with the residues of the binding pocket of the coronaviruses 3CLpro and exhibited better binding affinities toward the main protease than ritonavir and lopinavir. The top biflavonoids were further explored through molecular dynamics simulation, binding free energy calculation and residual energy contributions estimated by the MM-PBSA. Also, drug likeness property investigation by Swiss ADME tools and density functional theory (DFT) calculations were performed. The results confirmed that the 3CLpro-amentoflavone, 3CLpro-bilobetin, 3CLpro-ginkgetin, and 3CLpro-sotetsuflavone complexes possess a large amount of dynamic properties such as high stability, significant binding energy and fewer conformation fluctuations. Also, the pharmacokinetics and drug-likeness studies and HOMO-LUMO and DFT descriptor values indicated a promising result of the selected natural biflavonoids. Overall findings indicate that the apigenin-based biflavonoids may inhibit COVID-19 by significant interactions in the binding pocket and those results can pave the way in drug discovery although the effectiveness of these bioactive compounds should be further validated by in-vitro and in-vivo investigations. Communicated by Ramaswamy H. Sarma.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a pandemic viral disease caused by SARS-CoV-2 that generated serious damages for both the human population and the global economy. Therefore, it is currently considered as one of the most important global health problems of human societies and there is an urgent need for potent drugs or vaccines which can effectively combat this virus. The chymotrypsin-like protease (3CLpro) of SARS-CoV-2 plays a key role in the viral replication inside the host and thus is a promising drug target to design and develop effective antiviral drugs against SARS and other coronaviruses. This study evaluated some antiviral coumarin phytochemicals as potential inhibitors of coronaviruses 3CLpro by in silico approaches such as molecular docking, ADMET prediction, molecular dynamics simulation, and MM-PBSA binding energy calculation. Natural coumarin derivatives were docked to the 3CLpro of SARS-CoV-2 and for further investigation, docked to the 3CLpro of SARS-CoV and MERS-CoV. The docking scores of these natural compounds were compared with 3CLpro referenced inhibitors (ritonavir and lopinavir) and co-crystal inhibitor N3. Molecular docking studies suggested more than half of the coumarin phytochemicals had favorable interaction at the binding pocket of the coronaviruses 3CLpro and exhibited better binding affinities toward 3CLpro than ritonavir and lopinavir. Most antiviral phytochemicals interact strongly with one or both the catalytic dyad residues (His41 and Cys145) and the other key residues of SARS-CoV-2 main protease. Further, MD simulation and binding free energy calculations using MM-PBSA were carried out for three 3CLpro-coumarin complexes and 3CLpro-N3/lopinavir. The results confirmed that the 3CLpro-glycycoumarin, 3CLpro-oxypeucedanin hydrate, and 3CLpro-inophyllum P complexes were highly stable, experience fewer conformation fluctuations and share a similar degree of compactness. Also, the pharmacokinetics and drug-likeness studies showed good results for the selected coumarin phytochemicals.Therefore, the coumarin phytochemicals could be used as antiviral agents in the treatment of COVID-19 after further studies.