Multi-level scoring approach to discover multi-targeting potency of medicinal plant phytochemicals against protein targets in SARS-CoV-2 and human ACE-2 receptor

SARS-CoV-2 pandemic has become a major threat to human healthcare and world economy. Due to the rapid spreading and deadly nature of infection, we are in a situation to develop quick therapeutics to combat SARS-CoV-2. In this study, we have adopted a multi-level scoring approach to identify multi-targeting potency of bioactive compounds in selected medicinal plants and compared its efficacy with two reference drugs, Nafamostat and Acalabrutinib which are under clinical trials to treat SARS-CoV-2. In particular, we employ molecular docking and implicit solvent free energy calculations (as implemented in the Molecular Mechanics -Generalized Born Surface Area approach) and QM fragmentation approach for validating the potency of bioactive compounds from the selected medicinal plants against four di?erent viral targets and one human receptor (Angiotensin-converting enzyme 2 -ACE-2) which facilitates the SARS-CoV-2entry into the cell. The protein targets considered for the study are viral 3CL main protease (3CLpro), papain-like protease (PLpro), RNA dependent RNA polymerase (RdRp), and viral spike protein-human hACE-2 complex (Spike:hACE2)including human protein target (hACE-2). Herein, thereliable multi-level scoring approach was used to validate the mechanism behind the multi-targeting potency of selected phytochemicals from medicinal plants. The present study evidenced that the phytochemicals Chebulagic acid, Stigmosterol, Repandusinic acid and Geranin exhibited efficient inhibitory activity against PLpro while Chebulagic acid was highly active against 3CLpro. Chebulagic acid andGeranin also showed excellent target specific activity against RdRp.Luteolin, Quercetin, Chrysoeriol and Repandusinic acid inhibited the interaction of viral spike protein with human ACE-2 receptor. Moreover Piperlonguminine and Piperine displayed significant inhibitory activity against human ACE-2 receptor. Therefore, the identified compounds namely Chebulagic acid, Geranin and Repandusinic acid can serve as potent multi-targeting phytomedicine for treating COVID-19

Post-acute sequelae of SARS-CoV-2 Delta variant infection: A report of three cases in a single family

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that has resulted in global pandemic and crisis in health care system. Several studies have focused only on hospitalized patients with 30 to 90 days after one cycle of illness but post-acute sequelae of COVID-19 existing even after a year remains unclear. Moreover, long-term sequelae in outpatients have not been documented and henceforth myriad clinical sequelae in long haulers continue to evolve. In this study, we report three cases represents a single family presenting several post-acute sequelae one after the other extending beyond one year of recovery. To our knowledge such a case series has not been reported in earlier studies. Herein, we present the sequelae in various organs namely neuropsychiatric (tinnitus, anxiety, depression, insomnia, and posttraumatic stress disorder, cognitive decline), cardiovascular (tachycardia, bradycardia), gastrointestinal (appendicitis) and Dermatologic (erythematous rash and acne) besides ophthalmic manifestations (conjunctivitis and dry eyes) in Long-COVID-19 and recommend management strategies.