Tryptanthrin for COVID-19

Abstract To date, COVID-19 continues to pose a global health challenge, with substantial morbidity, mortality, and long-term post-COVID-19 complications threatening public health resilience. During the early pandemic, the IL-6 inhibitor (tocilizumab) was the widely used approved immunotherapy for critically ill patients; however, a subset of ICU cases exhibited normal interleukin-6 (IL-6) levels and failed to respond. We hypothesized that interleukin-17 (IL-17), which acts synergistically with IL-6, contributes to cytokine storm progression and severe inflammation. Our study uniquely integrates a clinical cross-sectional analysis with advanced in-silico modelling, directly linking patient-derived biomarker, radiological, and statistical data to molecular-level mechanisms of COVID-19 severity. Serum IL-17 was significantly elevated in critical versus moderate COVID-19 cases, with a threshold of 187.9 ng/mL predicting poor outcomes by ROC analysis. Logistic regression identified age and monocytes as independent predictors of severity, supporting a combined biomarker approach for improving the prognosis and clinical outcomes. Radiological findings, including ground-glass opacities and consolidations, alongside hematological abnormalities, were more frequent in critical cases. Computational docking revealed key amino acid residues—particularly asparagine (Asn) and cysteine (Cys)—as structural determinants shared by SARS-CoV-2 spike protein and human inflammatory mediators (IL-17R, IL-6R, CD41/CD61, CD47/SIRP). Asparaginase (ASNase) targeted critical residues such as the invariant gate residue “Asn343” and Cys213 of spike protein, Asn240 of IL-17R, and Asn136 of IL-6R. Several phytochemicals, including phytic acid and amygdalin, as well as synthetic agents such as candesartan, remdesivir, and enalapril, were found to preferentially bind to cysteine (Cys) residues—and, to a lesser extent, asparagine (Asn) residues—within key binding interfaces, in addition to targeting B-cell epitopes. This conserved residue preference supports the rationale for a dual-action therapeutic strategy in which asparaginase (ASNase) is combined with selected plant-derived ligands to simultaneously disrupt viral entry mechanisms and attenuate the inflammatory signalling. This dual-perspective approach not only identified IL-17 and IL-6 as independent severity predictors but also revealed conserved Asn and Cys motifs as critical therapeutic targets, leading to novel strategies—such as ASNase, synthetic agents and phytochemical combinations—for simultaneously blocking viral entry and modulating hyperinflammatory pathways. These findings warrant rigorous experimental and clinical validation to facilitate translation into effective therapeutic interventions.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

Amid the SARS‐CoV‐2 pandemic, herbal medicines have received much attention in its evidence-based therapeutics. Scientists across the globe are integrating new research at an unprecedented fast pace for the discovery of novel molecules against this deadly viral disease. Ever since ancient times, phytochemicals have long been used traditionally for the cure of many viral diseases and lately many are being tested for their potential against the viral replications/transcriptions. The unmatched structural diversity of phytoconstituents may prove to be a gold mine for antiviral drug discovery. Many plants like Heteromorpha spp., Bupleurum spp, Scrophularia scorodonia, Artemisia annua, Pyrrosia lingua, Lycoris radiate, and Lindera agregata have also been reported to have antiviral potential against SARS-CoV. Recently many synthetic molecules like remdesivir, tocilizumab, favipirapir, dexamethasone, glucocorticoid, and hydroxychloroquine etc. have been extensively investigated for their potential against the SARS‐CoV‐2, likewise, various plant-based molecules such as scutellarein, silvestrol, tryptanthrin, saikosaponin B2, quercetin, myricetin, caffeic acid, psoralidin, isobavachalcone, and lectins-griffiths in were also found to be equally effective. Needless to mention that, the herbal medicines are a valuable and powerful source of chemical compounds which need further chemical modifications and appropriate in-vitro and in-vivo testings for establishing their safety and efficacy as potential drugs against the battle with coronavirus pandemic. In this review, we will try to highlight the potential phytochemicals candidates with their possible molecular targets against the SARS‐CoV‐2and demystify the myths behind the purported remedies such as herbal therapies, teas, essential oils, tinctures, and silver products such as colloidal silver that have no scientific evidence to prevent or cure COVID-19. Apart from that, this review will also de-fabricate the surgency of objectionable claims that are continuously reckoning towards the treatment of COVID-19 with hundred per cent surety and are propagated by several herbal firms.