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The COVID‐19 outbreak poses a significant threat to the world's human population in 2020. Finding new drugs rapidly during this pandemic is quite challenging. Thus, in silico drug screening experiments may provide effective therapeutic alternatives for better assessing natural remedies in preventing and treating COVID‐19. The main protease (Mpro) is an important drug target that is essential and ubiquitous for the survival of SARS‐CoV‐2. In this study, we performed in silico high‐throughput virtual screening to identify potential hits employing a database of 3 million natural compounds (supernatural‐II database). The initially obtained top 100 virtual hits were subjected to a standard SP and XP docking protocol, achieving the top 30 hits. Compounds SN00340755 (glide score: −16.0 kcal/mol and ΔGbind: −134.29 kcal/mol) and SN00213037 (glide score: −13.30 kcal/mol and ΔGbind: −81.18 kcal/mol) exhibited significant binding energy against Mpro (PDB ID: 6XQS). The ligands SN00340755 and SN00213037 formed multiple hydrogen bonds with the catalytic residues, especially with the functionally important residue GLU166, which plays a significant role in protomer dimerization. Further post‐docking minimization studies (MM‐GBSA) were performed to estimate the ligand‐protein affinity. From MM‐GBSA studies, it was observed that Coulombic (−140.70 to −37.66 kcal/mol) and van der Waals (−79.32 to −20.59 kcal/mol) energies, favoring the binding of ligands to the Mpro target protein. The ADMET properties were predicted using Qikprop, Chem Axon, and Data Warrior tools, demonstrating the beneficial pharmacokinetic parameters of these natural compounds. The 100 ns molecular dynamics simulation study revealed minor protein fluctuations, indicating the stability of the protein‐ligand complex. [ABSTRACT FROM AUTHOR]

The second wave of coronavirus disease 2019 (COVID-19) caused severe infections with high mortality. An increase in the cases of COVID-19-associated mucormycosis (CAM) was reported predominantly in India. Commonly present in immunocompromised individuals, mucormycosis is often a life-threatening condition. Confounding factors and molecular mechanisms associated with CAM are still not well understood, and there is a need for careful research in this direction. In this review, a brief account of the diagnosis, management, and advancement in drug discovery for mucormycosis has been provided. Here, we summarize major factors that dictate the occurrence of mucormycosis in COVID-19 patients through the analysis of published literature and case reports. Major predisposing factors to mucormycosis appear to be uncontrolled diabetes, steroid therapy, and certain cancers. At the molecular level, increased levels of iron in COVID-19 might contribute to mucormycosis. We have also discussed the potential role and regulation of iron metabolism in COVID-19 patients in establishing fungal growth. Other factors including diabetes prevalence and fungal spore burden in India as contributing factors have also been discussed. [ABSTRACT FROM AUTHOR]

The recent coronavirus outbreak has changed the world's economy and health sectors due to the high mortality and transmission rates. Because the development of new effective vaccines or treatments against the virus can take time, an urgent need exists for the rapid development and design of new drug candidates to combat this pathogen. Here, we obtained antiviral peptides obtained from the data repository of antimicrobial peptides (DRAMP) and screened their predicted tertiary structures for the ability to inhibit the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using multiple combinatorial docking programs, including PatchDock, FireDock, and ClusPro. The four best peptides, DRAMP00877, DRAMP02333, DRAMP02669, and DRAMP03804, had binding energies of −1125.3, −1084.5, −1005.2, and −924.2 Kcal/mol, respectively, as determined using ClusPro, and binding energies of −55.37, −50.96, −49.25, −54.81 Kcal/mol, respectively, as determined using FireDock, which were better binding energy values than observed for other peptide molecules. These peptides were found to bind with the active cavity of the SARS-CoV-2 main protease; at Glu166, Cys145, Asn142, Phe140, and Met165, in addition to the substrate-binding sites, Domain 2 and Domain 3, whereas fewer interactions were observed with Domain 1. The docking studies were further confirmed by a molecular dynamics simulation study, in which several descriptors, including the root-mean-square difference (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), radius of gyration (Rg), and hydrogen bond formation, confirmed the stable nature of the peptide–main protease complexes. Toxicity and allergenicity studies confirmed the non-allergenic nature of the peptides. This present study suggests that these identified antiviral peptide molecules might inhibit the main protease of SARS-CoV-2, although further wet-lab experiments remain necessary to verify these findings. [ABSTRACT FROM AUTHOR]