COVID-19 pandemic has created a healthcare crisis across the world and has put human life under life-threatening circumstances. The recent discovery of the crystallized structure of the main protease (M_pro) from SARS-CoV-2 has provided an opportunity for utilizing computational tools as an effective method for drug discovery. Targeting viral replication has remained an effective strategy for drug development. M_pro of SARS-COV-2 is the key protein in viral replication as it is involved in the processing of polyproteins to various structural and nonstructural proteins. Thus, M_pro represents a key target for the inhibition of viral replication specifically for SARS-CoV-2. We have used a virtual screening strategy by targeting M_pro against a library of commercially available compounds to identify potential inhibitors. After initial identification of hits by molecular docking-based virtual screening further MM/GBSA, predictive ADME analysis, and molecular dynamics simulation were performed. The virtual screening resulted in the identification of twenty-five top scoring structurally diverse hits that have free energy of binding (ΔG) values in the range of −26-06 (for compound AO-854/10413043) to −59.81 Kcal/mol (for compound 329/06315047). Moreover, the top-scoring hits have favorable AMDE properties as calculated using in silico algorithms. Additionally, the molecular dynamics simulation revealed the stable nature of protein-ligand interaction and provided information about the amino acid residues involved in binding. Overall, this study led to the identification of potential SARS-CoV-2 M_pro hit compounds with favorable pharmacokinetic properties. We believe that the outcome of this study can help to develop novel M_pro inhibitors to tackle this pandemic. Communicated by Ramaswamy H. Sarma

: Natural products and leads inspired by them have acted as a probe for successful drug discovery for many decades. Pain is an obnoxious sensory and emotional experience associated with potential tissue damage. It affects the quality of life of patients to a greater extent. Despite the availability of several agents targeting TRP receptors, none of them can proficiently alleviate neuropathic pain. TRPV1 is a prospective target for treating neuropathic pain as it is recognized to modulate the pain circuitry at the periphery and the central level. In this review, we have discussed several natural molecules, such as Capsaicinoids, Capsinoids, Piperine, Eugenol, Scutigeral, Ginsenosides, Cinnamaldehyde, Camphor, Shogaol, Gingerols, Zingerone, Allicin, Evodiamine, Allylisothiocyanate, Cannabidiol, Ricinoleic acid, Isovelleral, Capsazepine, Thapsigargin, Pellitorine, Yohimbine, Curcumin and some semi-synthetic analogues that activate TRPV1 channels and consequently, can be further harnessed for the treatment of neuropathic pain.