Background: Human coronavirus (SARS-CoV-2) is causing a pandemic with significant morbidity and mortality. As no effective novel drugs are available currently, drug repurposing is an alternative intervention strategy. Here we present an in silico drug repurposing study that implements successful concepts of computer-aided drug design (CADD) technology for repurposing known drugs to interfere with viral cellular entry via the spike glycoprotein (SARS-CoV-2-S), which mediates host cell entry via the hACE2 receptor. Methods: A total of 4015 known and approved small molecules were screened for interaction with SARS-CoV-2-S through docking studies and 15 lead molecules were shortlisted. Additionally, streptomycin, ciprofloxacin, and glycyrrhizic acid (GA) were selected based on their reported anti-viral activity, safety, availability and affordability. The 18 molecules were subjected to molecular dynamics (MD) simulation. Results: The MD simulation results indicate that GA of plant origin may be repurposed for SARS-CoV-2 intervention, pending further studies. Conclusions: Repurposing is a beneficial strategy for treating COVID-19 with existing drugs. It is aimed at using docking studies to screen molecules for clinical application and investigating their efficacy in inhibiting SARS-CoV-2-S. SARS-CoV-2-S is a key pathogenic protein that mediates pathogen-host interaction. Hence, the molecules screened for inhibitory properties against SARS-CoV-2-S can be clinically used to treat COVID-19 since the safety profile is already known.

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Due to the huge demand for health care facilities, there is a need for safe therapeutic intervention which can reduce the need for extensive health care support. In that regard, the current study was aimed at performing Phase 1 clinical trial to determine the safety of plant formulation in 24 healthy volunteers and Phase 2 trials in 100 COVID-19 patients to determine the tolerability and impact on the level of COVID 19 specific inflammatory markers. The outcomes of the Phase 1study have suggested the safe usage of plant formulation in humans and encouraged to conduct Phase 2 clinical trial. In the Phase 2 trial, the plant formulation was evaluated in 100 COVID-19 patients along with the standard of care. In Phase 1 single dose of 500 mg plant formulation capsule was used as an intervention, while 1gm thrice a day of plant formulation for 14 days was the testing dose for Phase 2. During the Phase 1 trial, no adverse event was observed and all organ systems were normal in function. During the Phase 2 trial, 100 patients underwent randomization, 50 were assigned to receive plant formulation, and 50 to receive placebo. Three patients in the placebo and two patients in the plant formulation group had dropped out from the study. Hence, the primary analysis population included 95 patients (48 allocated to plant formulation and 47 to placebo). The COVID 19 specific inflammatory markers improved faster and became normal in the plant formulation treatment group. In conclusion, the plant formulation (ATRICOV 452) has been found to be safe in phases 1 and 2.

Objective: Ivermectin is an FDA-approved, broad-spectrum anti-parasitic agent. It was originally identified as an inhibitor of interaction between the human 29 immunodeficiency virus-1 (HIV-1) integrase protein (IN) and the Importin (IMP) α/β1 30 heterodimers, which are responsible for IN nuclear import. Recent studies demonstrate that ivermectin is worthy of further consideration as a possible SARS-CoV-2 antiviral. Methods: We built the pathogen-host interactome and analyzed it using PHISTO. We compared Ivermectin and plant molecules for their interaction with Importin α3 (IMA3) using molecular docking studies. Results: A phytochemical ATRI001 with the lowest binding energy-7.290 Kcal/mol was found to be superior to Ivermectin with binding energy-4.946 Kcal/mol. Conclusion: ATRI001 may be a potential anti-SARS-CoV-2 agent; however, it requires clinical evaluation.

Investigations on plants are revealing the potential therapeutic benefits of medicinal herbs in treating immunological disorders. Nephrotic syndrome has emerged as an immunological disorder. Steroid dependence poses a therapeutic challenge in the management of nephrotic syndrome. Our pilot study compares the efficacy of an ayurvedic polyherbal preparation 'Shathavaryadi Yoga (NS001)' with oral cyclophosphamide in maintaining remission in steroid-dependent nephrotic syndrome.