Historically, plants have been sought after as bio-factories for the production of diverse chemical compounds that offer a multitude of possibilities to cure diseases. To combat the current pandemic coronavirus disease 2019 (COVID-19), plant-based natural compounds are explored for their potential to inhibit the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The present study is aimed at the investigation of antiviral action of several groups of phytoconstituents against SARS-CoV-2 using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and spike (S) glycoprotein receptor binding domain (RBD) to ACE2 (PDB code: 6M0J) of SARS-CoV-2. For binding affinity evaluation, the docking scores were calculated using the Extra Precision (XP) protocol of the Glide docking module of Maestro. CovDock was also used to investigate covalent docking. The OPLS3e force field was used in simulations. The docking score was calculated by preferring the conformation of the ligand that has the lowest binding free energy (best pose). The results are indicative of better potential of solanine, acetoside, and rutin, as Mpro and spike glycoprotein RBD dual inhibitors. Acetoside and curcumin were found to inhibit Mpro covalently. Curcumin also possessed all the physicochemical and pharmacokinetic parameters in the range. Thus, phytochemicals like solanine, acetoside, rutin, and curcumin hold potential to be developed as treatment options against COVID-19.

Objectives: Convalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. Design: Open-label, parallel-arm, phase II, multicentre, randomized controlled trial. Setting: Thirty-nine public and private hospitals across India. Participants: Hospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air). Intervention: Participants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome Measure: Composite of progression to severe disease (PaO2/FiO2<100) or all-cause mortality at 28 days post-enrolment. Results: Between 22 nd April to 14 th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. Interpretation: CP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.

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The current study was designed to investigate the effect of Citrus limon (L.) Burm. (Rutaceae) fruits, commonly known as lemon, in experimental liver damage. The ethanol extract of Citrus limon fruits was evaluated for its effects on experimental liver damage induced by carbon tetrachloride, and the ethyl acetate soluble fraction of the extract was evaluated on HepG2 cell line. The ethanol extract normalized the levels of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), and total and direct bilirubin, which were altered due to carbon tetrachloride intoxication in rats. In the liver tissue, treatment significantly reduced the levels of malondialdehyde (MDA), hence the lipid peroxidation, and raised the levels of antioxidant enzymes superoxide dismutase (SOD) and catalase. It improved the reduced glutathione (GSH) levels in treated rats in comparison with CCl 4 -intoxicated rats. In the histopathologic studies, treated animals exhibited restoration of the liver architecture toward normal. Three doses of ethanol extract (i.e., 150, 300, and 500 mg=kg) were evaluated. The effect seen was dose dependent, and the effect of the highest dose was almost equal to the standard silymarin. In the investigation carried out on human liver-derived HepG2 cell line, significant reduction in cell viability was observed in cells exposed to CCl 4 . A dose-dependent increase in the cell viability was observed when CCl 4 -exposed HepG2 cells were treated with different concentrations of ethyl acetate soluble fraction of the ethanol extract. The highest percentage viability of HepG2 cells was observed at a concentration of 100 mg=mL. The extract merits further investigation to identify the active principles responsible for the hepatoprotective effect. The results from the current investigation also indicate good correlation between the in vivo and in vitro studies.