Feasibility analysis and mechanism exploration of Rhei Radix et Rhizome−Schisandrae Sphenantherae Fructus (RS) against COVID-19

Abstract

<b>Introduction.</b> As a novel global epidemic, corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 brought great suffering and disaster to mankind. Recently, although significant progress has been made in vaccines against SARS-CoV-2, there are still no drugs for treating COVID-19. It is well known that traditional Chinese medicine (TCM) has achieved excellent efficacy in the treatment of COVID-19 in China. As a treasure-house of natural drugs, Chinese herbs offer a promising prospect for discovering anti-COVID-19 drugs.<b>Hypothesis/Gap Statement.</b> We proposed that <i>Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus</i> (RS) may have potential value in the treatment of COVID-19 patients by regulating immune response, protecting the cardiovascular system, inhibiting the production of inflammatory factors, and blocking virus invasion and replication processes.<b>Aim.</b> We aimed to explore the feasibility and molecular mechanisms of RS against COVID-19, to provide a reference for basic research and clinical applications.<b>Methodology.</b> Through literature mining, it is found that a Chinese herbal pair, RS, has potential anti-COVID-19 activity. In this study, we analysed the feasibility of RS against COVID-19 by high-throughput molecular docking and molecular dynamics simulations. Furthermore, we predicted the molecular mechanisms of RS against COVID-19 based on network pharmacology.<b>Results.</b> We proved the feasibility of RS anti-COVID-19 by literature mining, virtual docking and molecular dynamics simulations, and found that angiotensin converting enzyme 2 (ACE2) and 3C-like protease (3 CL pro) were also two critical targets for RS against COVID-19. In addition, we predicted the molecular mechanisms of RS in the treatment of COVID-19, and identified 29 main ingredients, 21 potential targets and 16 signalling pathways. Rhein, eupatin, (-)-catechin, aloe-emodin may be important active ingredients in RS. ALB, ESR1, EGFR, HMOX1, CTSL, and RHOA may be important targets against COVID-19. Platelet activation, renin secretion, ras signalling pathway, chemokine signalling pathway, and human cytomegalovirus infection may be important signalling pathways against COVID-19.<b>Conclusion.</b> RS plays a key role in the treatment of COVID-19, which may be closely related to immune regulation, cardiovascular protection, anti-inflammation, virus invasion and replication processes.