In Silico Evaluation of Promising Naturally Occurring Bioactive Ligands Against Molecular Targets of SARS-Cov-2

• Published in: National Academy of Sciences, India. Proceedings. Section B. Biological Sciences Vol. 94; no. 2; pp. 251 - 260
• Main Authors: Soni, Unnati, Mishra, Tripti, Gupta, O. P., Pal, Mahesh, Gupta, Shalini, Singh, Saurabh Pratap, Sangwan, Amita, Misra, Krishna
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New Delhi Springer India 01.04.2024; Springer Nature B.V
• Subjects: Affinity; Behavioral Sciences; Bioactive compounds; Biomedical and Life Sciences; Coronaviruses; COVID-19; Curcumin; Drug development; Enzymes; Immune system; Immunosuppressive agents; Ivermectin; Life Sciences; Molecular dynamics; Nucleic Acid Chemistry; Plant Biochemistry; Proteins; Research Article; Severe acute respiratory syndrome coronavirus 2; Simulation; Spike protein; SARS-CoV-2; Mpro; Apigenin and curcumin; Spike proteins; RdRp; Derivatives of quercetin; TMPRSS2; ACE-2
• ISSN: 0369-8211; 2250-1746
• DOI: 10.1007/s40011-023-01496-x

The fatal virus SARS-CoV-2 emerged in December 2019, which caused a global pandemic of coronavirus disease, also known as COVID-19. Identification of the naturally occurring bioactive compounds that can inhibit or modulate the proteins and enzymes of the virus SARS-CoV-2 by targeting the host cells and immune system of the human body is an instrumental approach for COVID-19 therapy. It is an attempt to assess the potential of naturally occurring bioactive compounds and their derivatives against coronavirus using molecular docking and molecular dynamics simulation studies, i.e. binding affinity of the active receptors of the host cells to the selected bioactive compound against SARS-CoV-2. Docking and MD simulation studies were carried out in this study to estimate the affinity of the selected bioactive compounds along with the reference drugs remdesivir and ivermectin in opposition to the vital target proteins and enzymes of coronavirus. Among all selected bioactives, as per the computational docking parameters, curcumin has shown excellent binding, especially against ACE-2 and RdRp. Apigenin also showed encouraging results against spike protein comparable to reference drugs remdesivir and ivermectin. These results are furthermore established by the molecular dynamic simulation study and analysis of protein–ligand complex, which shows minimum binding deviation and minor average fluctuations in energies of protein residues throughout the simulation period. Curcumin glucuronide and apigenin 7-glucoside showed the most suitable response as they have a marvellous binding affinity with COVID-19 targets that are responsible for viral entry as well as their further replication into the host cell; hence, they could be some possible potential drug candidates for COVID-19 therapy.