Virtual screening of phytochemicals by targeting multiple proteins of severe acute respiratory syndrome coronavirus 2: Molecular docking and molecular dynamics simulation studies.

OBJECTIVE: Medicinal herbs are being investigated for medicationhg development against SARS-CoV-2 as a rich source of bioactive chemicals. One of the finest approaches for finding therapeutically effective drug molecules in real time is virtual screening scheme such as molecular docking in conjunction with molecular dynamics (MD) simulation. These virtual techniques provide an ample opportunity for the screening of plausible inhibitors of SARS-CoV-2 different target proteins from a comprehensive and extensive phytochemical library. The study was designed to identify potential phytochemicals by virtual screening against different receptor proteins. METHODS: In the current study, a library of plant secondary metabolites was created by manually curating 120 phytochemicals known to have antimicrobial as well as antiviral properties. In the current study, different potential phytochemicals were identified by virtual screening against various selected receptor proteins (i.e., viral main proteases, RNA-dependent RNA polymerase (RdRp), ADP ribose phosphatase, nonstructural proteins NSP7, NSP8, and NSP9) which are key proteins responsible for transcription, replication and maturation of SARS-CoV-2 in the host. Top three phytochemicals were selected against each viral receptor protein based on their best S-scores, RMSD values, molecular interactions, binding patterns and drug-likeness properties. RESULTS: The results of molecular docking study revealed that phytochemicals (i.e., baicalin, betaxanthin, epigallocatechin, fomecin A, gallic acid, hortensin, ichangin, kaempferol, limonoic acid, myricetin hexaacetat, pedalitin, quercetin, quercitrin, and silvestrol) have strong antiviral potential against SARS-CoV-2. Additionally, the reported preeminent reliable phytochemicals also revealed toxicity by no means during the evaluation through ADMET profiling. Moreover, the MD simulation study also exhibited thermal stability and stable binding affinity of the pedalitin with SARS-CoV-2 RdRp and SARS-CoV-2 main protease which suggests appreciable efficacy of the lead optimization. CONCLUSION: The biological activity and pharmacologically distinguishing characteristics of these lead compounds also satisfied as repurposing antiviral drug contenders and are worth substantial evaluation in the biological laboratory for the recommendation of being plausible antiviral drug candidates against SARS-CoV-2.

Unraveling the mystery of efficacy in Chinese medicine formula: New approaches and technologies for research on pharmacodynamic substances.

Traditional Chinese medicine (TCM) is the key to unlock treasures of Chinese civilization. TCM and its compound play a beneficial role in medical activities to cure diseases, especially in major public health events such as novel coronavirus epidemics across the globe. The chemical composition in Chinese medicine formula is complex and diverse, but their effective substances resemble "mystery boxes". Revealing their active ingredients and their mechanisms of action has become focal point and difficulty of research for herbalists. Although the existing research methods are numerous and constantly updated iteratively, there is remain a lack of prospective reviews. Hence, this paper provides a comprehensive account of existing new approaches and technologies based on previous studies with an in vitro to in vivo perspective. In addition, the bottlenecks of studies on Chinese medicine formula effective substances are also revealed. Especially, we look ahead to new perspectives, technologies and applications for its future development. This work reviews based on new perspectives to open horizons for the future research. Consequently, herbal compounding pharmaceutical substances study should carry on the essence of TCM while pursuing innovations in the field.