Plant formulation ATRICOV 452 in improving the level of COVID-19 specific inflammatory markers in patients.

Importance: Due to the huge demand for healthcare facilities, there is a need for safe therapeutic intervention which can reduce the need for extensive healthcare support. Objective: In phase 1, to determine the safety of plant formulation in healthy volunteers and in phase 2, to validate its potential to improve the level of COVID-19 specific inflammatory markers. Design: Setting, and Participants: The phase 1 single fasting dose study was conducted on 24 healthy adult human volunteers to evaluate the safety and tolerability of plant formulation. The usage of plant formulation in humans was found safe and encouraged conducting Phase 2 clinical trial to evaluate the efficacy in 100 COVID-19 patients along with the standard of care. Interventions: Phase 1: plant formulation capsule of 500 mg single dose; Phase 2: plant formulation 1 gm thrice a day for 14 days. Results: 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 of 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. No one needed hospital care or oxygen. Conclusions: and Relevance: The investigational product, plant formulation (ATRICOV 452) has been found to be safe in phases 1 and 2. Further, in the phase 2 trial, ATRICOV 452 was effective at the dose of 1 mg, three times a day dose frequency to improve the level of COVID-19 specific inflammatory markers. Trial registration: Phase 1: CTRI Registration number: CTRI 2020/09/027660 Phase 2: CTRI Registration number: CTRI/2021/01/030795.

In silico, in vitro screening of plant extracts for anti-SARS-CoV-2 activity and evaluation of their acute and sub-acute toxicity

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In silico screening of known small molecules to bind ACE2 specific RBD on Spike glycoprotein of SARS-CoV-2 for repurposing against COVID-19.

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.