Integrating biochemical, computational, and randomized clinical trials to evaluate the efficacy of herbal formulation...

The coronavirus disease 2019 (COVID-19) pandemic has prompted extensive research into therapeutic options, including traditional ayurvedic medicine. This study aims to investigate the safety and efficacy of herbal formulation through in vitro, in silico, and clinical trials. An in vitro antiviral assay was performed using a plaque assay to evaluate the percentage of virus inhibition. In silico analysis utilized AutoDock 4.2.6 to assess binding affinities of 95 active ingredients in the formulation against key severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets, including Papain-like protease, RNA-dependent RNA polymerase, nucleocapside proteins, non-structural protein-1, and open reading frame 6. The first trial was an open-label study involving 60 subjects, where 30 received the test formulation alongside standard treatment, while the other 30 received standard treatment alone. This was followed by a double-blind trial with 60 participants randomly assigned to receive either the test formulation or a placebo along with standard treatment. The in vitro assay indicated that the herbal formulation reduced viral load by 94.51% at 48 hpi. In silico analysis revealed that phyto-compounds demonstrated stronger binding energies with target proteins than remdesivir. Clinical trials showed significant reductions in disease progression and symptom alleviation; an open-label trial recorded a recovery rate of 96.7%, while a double-blind trial reported a recovery rate of 93.3% within 7 days and 100% recovery rate recorded within 10 days in both trials. Notably, the formulation reduced the inflammatory markers and enhanced the immune responses. The herbal formulation showed potent antiviral activity in vitro and strong molecular binding with key SARS-CoV-2 proteins in silico. Clinical data demonstrated accelerated recovery and improved immune modulation, highlighting the formulation's therapeutic potential as a complementary option for COVID-19 management. The herbal formulation demonstrated its potential as an effective adjuvant therapy for COVID-19, supported by comprehensive preclinical, computational, and clinical evidence. This study underscores the integration of novel herbal formulation with contemporary scientific methodologies to address global health challenges effectively. Clinical trial numbers: Clinical Trials Registry of India (CTRI/2020/05/025340; CTRI/2021/06/034132).