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Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19).

ABSTRACT: The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions.

SUBMITTER: Nadeem MS

PROVIDER: S-EPMC7238035 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19).

Nadeem Muhammad Shahid MS Zamzami Mazin A MA Choudhry Hani H Murtaza Bibi Nazia BN Kazmi Imran I Ahmad Habib H Shakoori Abdul Rauf AR

Pathogens (Basel, Switzerland) 20200422 4

The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. Accord ...[more]

PMID: 32331255

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Project description:The ongoing pandemic coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern. Environmental factors such as air pollution and smoking and comorbid conditions (hypertension, diabetes mellitus and underlying cardio-respiratory illness) likely increase the severity of COVID-19. Rheumatic manifestations such as arthralgias and arthritis may be prevalent in about a seventh of individuals. COVID-19 can result in acute interstitial pneumonia, myocarditis, leucopenia (with lymphopenia) and thrombocytopenia, also seen in rheumatic diseases like lupus and Sjogren's syndrome. Severe disease in a subset of patients may be driven by cytokine storm, possibly due to secondary hemophagocytic lymphohistiocytosis (HLH), akin to that in systemic onset juvenile idiopathic arthritis or adult-onset Still's disease. In the absence of high-quality evidence in this emerging disease, understanding of pathogenesis may help postulate potential therapies. Angiotensin converting enzyme 2 (ACE2) appears important for viral entry into pneumocytes; dysbalance in ACE2 as caused by ACE inhibitors or ibuprofen may predispose to severe disease. Preliminary evidence suggests potential benefit with chloroquine or hydroxychloroquine. Antiviral drugs like lopinavir/ritonavir, favipiravir and remdesivir are also being explored. Cytokine storm and secondary HLH might require heightened immunosuppressive regimens. Current international society recommendations suggest that patients with rheumatic diseases on immunosuppressive therapy should not stop glucocorticoids during COVID-19 infection, although minimum possible doses may be used. Disease-modifying drugs should be continued; cessation may be considered during infection episodes as per standard practices. Development of a vaccine may be the only effective long-term protection against this disease.Key Points• Patients with coronavirus disease 19 (COVID-19) may have features mimicking rheumatic diseases, such as arthralgias, acute interstitial pneumonia, myocarditis, leucopenia, lymphopenia, thrombocytopenia and cytokine storm with features akin to secondary hemophagocytic lymphohistiocytosis.• Although preliminary results may be encouraging, high-quality clinical trials are needed to better understand the role of drugs commonly used in rheumatology like hydroxychloroquine and tocilizumab in COVID-19.• Until further evidence emerges, it may be cautiously recommended to continue glucocorticoids and other disease-modifying antirheumatic drugs (DMARDs) in patients receiving these therapies, with discontinuation of DMARDs during infections as per standard practice.

Project description:For the initial phase of pandemic of coronavirus disease 2019 (COVID-19), repurposing drugs that in vitro inhibit severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been attempted with overlooked or overestimated efficacy owing to limited clinical evidence. Most early clinical trials have the defects of study design, small sample size, non-randomized design, or different timings of treatment initiation. However, well-designed studies on asymptomatic or mild, or pediatric cases of COVID-19 are scarce and desperately needed to meet the clinical need. However, a trend could be observed based on current clinical evidence. Remdesivir and favipiravir may shorten the recovery time; lopinavir/ritonavir does not demonstrate treatment efficacy in severe patients. Triple therapy of ribavirin, lopinavir, and interferon ?-1b showed early viral negative conversion, and the major effect may be related to interferon. Some small sample-size studies showed that interleukin-6 inhibitors may demonstrate clinical improvement; non-critical patients may benefit from convalescent plasma infusion in small sample-size studies; and the role of hydroxychloroquine or chloroquine in the treatment and prophylaxis of COVID-19 remains unclear. Combination therapy of traditional Chinese medicine with antiviral agents (ex. interferon, lopinavir, or arbidol) may alleviate inflammation in severe COVID-19 patients based on small sample-sized observational studies and experts' opinion. Most of the published studies included severe or critical patients with COVID-19. Combination therapy of antiviral agents and immune-modulating drugs is reasonable especially for those critical COVID-19 patients with cytokine release syndrome. Drugs to blunt cytokine release might not benefit for patients in the early stage with mild disease or the late stage with critical illness. Traditional Chinese medicine with antiviral effects on SARS-CoV-2 and immune-modulation is widely used for COVID-19 patients in China, and is worthy of further studies. In this review, we aim to highlight the available therapeutic options for COVID-19 based on current clinical evidence and encourage clinical trials specific for children and for patients with mild disease or at the early stage of COVID-19.

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Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19).

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Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19).

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