Angiotensin converting enzyme 2 (ACE2) and main protease (M Pro ) are significant target proteins, mainly involved in the attachment of viral genome to host cells and aid in replication of severe acute respiratory syndrome‐coronaviruses or SARS‐CoV genome. In the present study, we identified 11 potent bioactive compounds from ethanolic leaf extract of Ipomoea obscura (L.) by using GC‐MS analysis. These potential bioactive compounds were considered for molecular docking studies against ACE2 and M Pro target proteins to determine the antiviral effects against SARS‐COV. Results exhibits that among 11 compounds from I. obscura (L.), urso‐deoxycholic acid, demeclocycline, tetracycline, chlorotetracycline, and ethyl iso‐allocholate had potential viral inhibitory activity. Hence, the present findings suggested that chemical constitution present in I. obscura (L.) will address inhibition of corona viral replication in host cells.

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COVID-19 is a viral pandemic caused by SARS-CoV-2. Due to its highly contagious nature, millions of people are getting affected worldwide knocking down the delicate global socio-economic equilibrium. According to the World Health Organization, COVID-19 has affected over 186 million people with a mortality of around 4 million as of July 09, 2021. Currently, there are few therapeutic options available for COVID-19 control. The rapid mutations in SARS-CoV-2 genome and development of new virulent strains with increased infection and mortality among COVID-19 patients, there is a great need to discover more potential drugs for SARS-CoV-2 on a priority basis. One of the key viral enzymes responsible for the replication and maturation of SARS-CoV-2 is M pro protein. In the current study, structure-based virtual screening was used to identify four potential ligands against SARS-CoV-2 M pro from a set of 8,722 ASINEX library compounds. These four compounds were evaluated using ADME filter to check their ADME profile and druggability, and all the four compounds were found to be within the current pharmacological acceptable range. They were individually docked to SARS-CoV-2 M pro protein to assess their molecular interactions. Further, molecular dynamics (MD) simulations was carried out on protein–ligand complex using Desmond at 100 ns to explore their binding conformational stability. Based on RMSD, RMSF and hydrogen bond interactions, it was found that the stability of protein–ligand complex was maintained throughout the entire 100 ns simulations for all the four compounds. Some of the key ligand amino acid residues participated in stabilizing the protein–ligand interactions includes GLN 189, SER 10, GLU 166, ASN 142 with PHE 66 and TRP 132 of SARS-CoV-2 M pro . Further optimization of these compounds could lead to promising drug candidates for SARS-CoV-2 M pro target.

Cervical cancer, one of the most common causes of cancer-related death among women in the world, has been linked to the presence of a particular oncoprotein that is predominantly transferred through sexual contact with an infected host. In 90% of cervical cancer deaths, a correlation has been found with the expression of the viral genome of HPV16 E6. As a result, HPV16 E6 has emerged as an optimistic therapeutic drug target for the treatment of cervical cancer. In order to develop a drug that is capable of disturbing the genome expression activity of HPV16 E6, it is imperative to identify the key chemical features of its known inhibitors. In this study, we present an investigationon identifying potential inhibitors of HPV16 E6 by utilizing pharmacophore-based virtual screening, molecular docking, ADME prediction, and molecular dynamics simulation. In the initial stage, we generated a ligand-based pharmacophore model based on the features of four known HPV16 E6 inhibitors (CA24, CA25, CA26, and CA27)via the PHASE module implanted in the Schrödinger suite. We constructedfour-point pharmacophore features, which consists of three hydrogen bond acceptors (A) and one aromatic ring (R). The common pharmacophore features further employed as a query for virtual screening against the ASINEX database via the Schrödinger suite. The pharmacophore-based virtual screening filtered out top 2000 hits, based on the fitness score. We applied the molecular docking studies for further compound filtration using Glide which provide three ligand filtering phases, namely HTVS, SP, XP. Initially, 1000 compounds were obtained from HTVS docking. Based on the glide score, they were further filtered to 500 hits by employing docking in standard precision mode. Finally, the best four hits were identified using docking in XP mode. The four compounds were then further subjected to ADME profile prediction by engaging the Qikprop module. The ADME properties of the four fell within a satisfactory range and the compounds exhibited anticipated pharmacokinetic properties. These compounds were further investigated to determine the binding stability of the protein-ligand complex at a different time scale (100 ns) by using the desmond package for a molecular dynamics simulation. These molecular dynamics simulation studies revealed that theCYS 51 and GLN 107 proteins are residues of HPV 16 E6 binding sites, and the root mean square deviation (RMSD) and root mean square fluctuations (RMSF) values for these residues were also found to be within satisfactory ranges and suggest a crucial role in enhancing the stability of the protein-ligand complex during the simulation. From these computational investigations, we concluded that the four potential compounds are appropriate for further study, and potential clinical investigation, as HPV16 E6 inhibitors.

One of the major public health problems globally, malaria, is mainly caused protozoan parasites from the genus Plasmodium, and commonly spreads to people through the bites of infected female mosquitoes of the genus Anopheles. Strategies for treatment, prevention, and control are available for malaria but the eradication of malaria still poses great challenge due to plasmodium’s drug resistance over the past decades. Development of novel antimalarial drugs remains a significant task to protect people from malaria. N-Myristoyl transferase is responsible for the N-Myristoylation catalysis process and the survival of Plasmodium species. Thus, it is considered a therapeutic drug target in protozoans and was recently validated as a significant target for Plasmodium vivax. In this present scenario, we endeavour to identify effective NMT inhibitors to prevent the onset of malaria in the human species. Initially, the structure-based virtual screening was executed against ZINC database and four potential candidates for NMT were identified. Furthermore, the four identified compounds were subjected to ADME prediction and all the four compounds found within adequate range with predicted ADME properties. Eventually, we conducted the molecular dynamics simulation to investigate the binding stability of top three protein-ligand complexes at different time scale by employing the tool Desmond. The molecular dynamics simulation studies revealed the protein-ligand complexes were stable throughout the entire simulation. Besides, we noticed that the residues ASN 365, PHE 103 and HIS 213 of NMT were crucially involved in the formation of various intermolecular interactions, significantly contributing to the stability of protein-ligand complexes. From this computational investigation, we suggest that the three identified potential compounds are extremely useful for further lead optimization and drug development.