Tinospora cordifolia for COVID-19

Abstract The rapid transmission of SARS-CoV-2 and its capability to spread in humans has brought about the development of new approaches for treatment against COVID-19. Drugs and vaccines available currently either target the virus ectodomain or endodomain. Thus, repurposing the use of natural products that target more than one part of the virus is the fastest option available for treatment. Plants are a repository of important constituents with proven significant efficacy against many human viruses. The present study focused on employing computational approaches for screening phytochemicals from 4 Indian medicinal plants, by targeting more than one part of SARS-CoV-2 for the identification of natural antiviral therapeutics to determine their feasibility as potential inhibitors of target viral proteins. Here, we used a multi-target, ligand virtual screening study on 9 target proteins important in SARS-CoV-2 lifecycle, namely Spike glycoprotein, Nucleocapsid phosphatase, Spike protein ACE-2, Non-structural protein 10 and 12, RdRp, Envelope protein, Main protease/3CL protease, and Papain like proteas. Out of the 58 plant phytochemicals screened, Z-5-methyl-6- heneicosen-11- one from Piper nigrum, Arjunetin from Terminalia arjuna, Rutin from Azadirachta indica and Makisterone A from Tinospora cordifolia exhibited highest binding affinity with 9 viral targets. In addition, ADMET analysis indicated Ursodeoxycholic acid, Ellagic Acid, Epicatechin and Isocolumbin, Ecdysterone, Columbin from Piper nigrum, Terminalia arjuna, Azadirachta indica, and Tinospora cordifolia have good binding energetics with the target viral proteins. The research thus enlightens the suitable pharmacological properties and the anti-viral activity of potential medicinal plant molecules for human administration using extensive in-silico techniques.

AbstractTo attain promising pharmacotherapies, researchers have applied drug repurposing (DR) techniques to discover the candidate medicines to combat the coronavirus disease 2019 (COVID-19) outbreak. Although many DR approaches have been introduced for treating different diseases, only structure-based DR (SBDR) methods can be employed as the first therapeutic option against the COVID-19 pandemic because they rely on the rudimentary information about the diseases such as the sequence of the severe acute respiratory syndrome coronavirus 2 genome. Hence, to try out new treatments for the disease, the first attempts have been made based on the SBDR methods which seem to be among the proper choices for discovering the potential medications against the emerging and re-emerging infectious diseases. Given the importance of SBDR approaches, in the present review, well-known SBDR methods are summarized, and their merits are investigated. Then, the databases and software applications, utilized for repurposing the drugs against COVID-19, are introduced. Besides, the identified drugs are categorized based on their targets. Finally, a comparison is made between the SBDR approaches and other DR methods, and some possible future directions are proposed.

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.

Abstract Background SARS-CoV-2 infections caused mild-to-moderate illness. However, a sizable portion of infected people experience a rapid progression of hyper-inflammatory and hypoxic respiratory illness that necessitates an effective and safer remedy to combat COVID-19. Methods A total of 150 COVID-19-positive patients with no to mild symptoms, between the age groups 19–65 years were enrolled in this randomized, open-labeled three-armed clinical trial. Among them, 136 patients completed the study with RT-PCR negative reports. The patients received herbal drugs orally (Group A (Adhatoda vasica; AV; 500 mg; n = 50); Group B (Tinospora cordifolia; TC; 500 mg; n = 43), and Group C (AV + TC; 250 mg each; n = 43)) for 14 days. Clinical symptoms, vital parameters, and viral clearance were taken as primary outcomes, and biochemical, hematological parameters, cytokines, and biomarkers were evaluated at three time points as secondary outcomes. Results We found that the mean viral clearance time was 13.92 days (95% confidence interval [CI] 12.85–14.99) in Group A, 13.44 days (95% confidence interval [CI] 12.14–14.74) in Group B, and 11.86 days (95% confidence interval [CI] 10.62–13.11) days in Group C. Over a period of 14 days, the mean temperature in Groups A, and B significantly decreased linearly. In Group A, during the trial period, eosinophils, and PT/INR increased significantly, while monocytes, SGOT, globulin, serum ferritin, and HIF-1α, a marker of hypoxia reduced significantly. On the other hand, in Group B hsCRP decreased at mid-treatment. Eosinophil levels increased in Group C during the treatment, while MCP-3 levels were significantly reduced. Conclusions All the patients of the three-armed interventions recovered from COVID-19 and none of them reported any adverse effects from the drugs. Group C patients (AV + TC) resulted in a quicker viral clearance as compared to the other two groups. We provide the first clinical report of AV herbal extract acting as a modifier of HIF-1α in COVID-19 patients along with a reduction in levels of ferritin, VEGF, and PT/INR as the markers of hypoxia, inflammation, and thrombosis highlighting the potential use in progression stages, whereas the TC group showed immunomodulatory effects. Trial registration Clinical Trials Database -India (ICMR-NIMS), CTRI/2020/09/028043. Registered 24th September 2020, https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=47443&EncHid=&modid=&compid=%27,%2747443det%27 Graphical Abstract

Abstract: The global impact of the COVID-19 pandemic caused by SARS-CoV-2 necessitates innovative strategies for the rapid development of effective treatments. Computational methodologies, such as molecular modelling, molecular dynamics simulations, and artificial intelligence, have emerged as indispensable tools in the drug discovery process. This review aimed to provide a comprehensive overview of these computational approaches and their application in the design of antiviral agents for COVID-19. Starting with an examination of ligand-based and structure-based drug discovery, the review has delved into the intricate ways through which molecular modelling can accelerate the identification of potential therapies. Additionally, the investigation extends to phytochemicals sourced from nature, which have shown promise as potential antiviral agents. Noteworthy compounds, including gallic acid, naringin, hesperidin, Tinospora cordifolia, curcumin, nimbin, azadironic acid, nimbionone, nimbionol, and nimocinol, have exhibited high affinity for COVID-19 Mpro and favourable binding energy profiles compared to current drugs. Although these compounds hold potential, their further validation through in vitro and in vivo experimentation is imperative. Throughout this exploration, the review has emphasized the pivotal role of computational biologists, bioinformaticians, and biotechnologists in driving rapid advancements in clinical research and therapeutic development. By combining state-of-the-art computational techniques with insights from structural and molecular biology, the search for potent antiviral agents has been accelerated. The collaboration between these disciplines holds immense promise in addressing the transmissibility and virulence of SARS-CoV-2.

The rapid spread of the new coronavirus disease (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Although specific vaccines are available and natural drugs are being researched, supportive care and specific treatments to alleviate symptoms and improve patient quality of life remain critical. Chinese medicine (CM) has been employed in China due to the similarities between the epidemiology, genomics, and pathogenesis of SARS-CoV-2 and SARS-CoV. Moreover, the integration of other traditional oriental medical systems into the broader framework of integrative medicine can offer a powerful approach to managing the disease. Additionally, it has been reported that integrated medicine has better effects and does not increase adverse drug reactions in the context of COVID-19. This article examines preventive measures, potential infection mechanisms, and immune responses in Western medicine (WM), as well as the pathophysiology based on principles of complementary medicine (CM). The convergence between WM and CM approaches, such as the importance of maintaining a strong immune system and promoting preventive care measures, is also addressed. Current treatment options, traditional therapies, and classical prescriptions based on empirical knowledge are also explored, with individual patient circumstances taken into account. An analysis of the potential benefits and challenges associated with the integration of complementary and Western medicine (WM) in the treatment of COVID-19 can provide valuable guidance, enrichment, and empowerment for future research endeavors.

Background. Since the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in discovering potential therapeutic agents for this disease. In this regard, we conducted a systematic review through an overview of drug development (in silico, in vitro, and in vivo) for treating COVID-19. Methods. A systematic search was carried out in major databases including PubMed, Web of Science, Scopus, EMBASE, and Google Scholar from December 2019 to March 2021. A combination of the following terms was used: coronavirus, COVID-19, SARS-CoV-2, drug design, drug development, In silico, In vitro, and In vivo. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure. Results. A total of 2168 articles were identified through searching databases. Finally, 315 studies (266 in silico, 34 in vitro, and 15 in vivo) were included. In studies with in silico approach, 98 article study repurposed drug and 91 studies evaluated herbal medicine on COVID-19. Among 260 drugs repurposed by the computational method, the best results were observed with saquinavir (n = 9), ritonavir (n = 8), and lopinavir (n = 6). Main protease (n = 154) following spike glycoprotein (n = 62) and other nonstructural protein of virus (n = 45) was among the most studied targets. Doxycycline, chlorpromazine, azithromycin, heparin, bepridil, and glycyrrhizic acid showed both in silico and in vitro inhibitory effects against SARS-CoV-2. Conclusion. The preclinical studies of novel drug design for COVID-19 focused on main protease and spike glycoprotein as targets for antiviral development. From evaluated structures, saquinavir, ritonavir, eucalyptus, Tinospora cordifolia, aloe, green tea, curcumin, pyrazole, and triazole derivatives in in silico studies and doxycycline, chlorpromazine, and heparin from in vitro and human monoclonal antibodies from in vivo studies showed promised results regarding efficacy. It seems that due to the nature of COVID-19 disease, finding some drugs with multitarget antiviral actions and anti-inflammatory potential is valuable and some herbal medicines have this potential.