Phytochemicals for mitigating the COVID-19 crisis: evidence from pre-clinical and clinical studies

Abstract

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019 quickly escalated to pandemic levels and had a severe impact on public health. There are 761 million confirmed coronavirus disease 2019 (COVID-19) cases, with over 6.88 million deaths worldwide till March 2023. Severe cases of the disease caused critical respiratory failure followed by multiorgan involvement. Clinical escalation of COVID-19 has been correlated with markedly increased plasma inflammatory markers [e.g., C-reactive protein (CRP)] and pro-inflammatory cytokine levels [e.g., interleukin (IL)-6, tumor necrosis factor-α (TNF-α)]. Therapeutic options have mostly utilized corticosteroids, antivirals (e.g., remdesivir), and monoclonal antibody-based immunomodulation (e.g., tocilizumab). These existing treatments have adverse side effects, inadequate efficacy, and limitations in administering to patients with comorbidities and other underlying diseases. Monoclonal antibody-based therapies and some of the antivirals are very costly. Many phytochemicals have previously reported anti-inflammatory, antiviral, and antioxidant properties. Studying the effectiveness of such phytochemicals against COVID-19 and identifying new plant-derived molecules with antiviral properties have been a focus since the SARS-CoV-2 outbreak. This review article has documented in vitro, in vivo, and clinical studies encompassing 28 different phytochemicals belonging to various chemical groups (e.g., polyphenols, alkaloids, terpenes) that show anti-COVID-19 activity. These findings suggest that multiple phytochemicals can interfere with virus entry and replication inside the host cell. Many of them can protect from cytokine storm by acting on intracellular signalling pathways in addition to inhibiting virus multiplication. Phytochemicals may prove useful in alleviating post-COVID complications associated with kidney injury, and central nervous system complications, as well. Plant-derived compounds are usually cheaper and have fewer side effects. But, developing new formulations with better absorption and bioavailability remains a priority. This review informs the readers of the current status and indicates the ongoing research in this highly relevant field.

Unravelling Insights into the Evolution and Management of SARS-CoV-2

“…Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin, and betulinic acid, which were proposed as SARS-CoV-2 inhibitors [159]. Regarding natural products, resveratrol, curcumin, and quercetin have demonstrated in vitro antiviral activity against SARS-CoV-2, and in vivo, a nebulised formulation has been demonstrated to alleviate the respiratory symptoms of COVID-19 [158,159,161].…”

Phytochemical-loaded Nanoparticles in COVID-19 Management

“…A randomized clinical trial exhibited reduction in the symptoms of COVID-19 on using the phytochemical hesperidin. In another clinical study on antiviral activity of curcumin, it was found that the administration of nano-curcumin capsule orally could significantly reduce mRNA expression of pro-inflammatory cytokines (Das et al, 2023). The phytochemical silymarin, effective against SARS-CoV-2, is in Phase 3 of clinical trial (NCT04394208) and is in the recruitment stage.…”