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Exploring Repurposing Potential of Existing Drugs in the Management of COVID-19 Epidemic: A Critical Review.

ABSTRACT: Despite high morbidity and mortality of ongoing coronavirus disease 2019 (COVID-19) pandemic, no specific therapy has been established till date. Though in vitro studies identified various molecules as possible therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these findings call for substantiation by human studies. We conducted this review aiming at reporting evidences on therapies used so far globally for management of COVID-19 in clinical settings. We searched electronic databases as PubMed, Google Scholar, EMBASE and extracted 612 possible studies as on May 31, 2020. We included original studies of any epidemiological design done on human COVID-19 patients and measured clinical outcomes. Finally, following removal of duplicates and studies meeting exclusion criteria, we derived 22 studies, of which eight were clinical trials, seven were case reports and case series, and seven were observational studies. The most reported therapies were hydroxychloroquine (HCQ) (eight studies) and lopinavir/ritonavir (four studies). We conclude from the evidence generated so far that interferon combined with antivirals, remdesivir, umifenovir and favipiravir were mostly associated with better clinical outcomes. The therapeutic effect of HCQ was established initially by two clinical trials; one of them showing a reinforcing effect by azithromycin but subsequent studies did not elicit any effectiveness rather increased rate of adverse events was reported. Lopinavir/ritonavir was found beneficial when administered with interferon and ribavirin, but one clinical trial on its sole use proved contrary. As many clinical trials are in process, we expect to get concrete evidences on repurposing of existing drugs based on less biased, high powered studies.

SUBMITTER: Chakraborty D

PROVIDER: S-EPMC7430870 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Exploring Repurposing Potential of Existing Drugs in the Management of COVID-19 Epidemic: A Critical Review.

Chakraborty Debjit D Debnath Falguni F Biswas Subrata S Bhatta Mihir M Ganguly Suman S Deb Alok Kumar AK Saha Malay Kumar MK Dutta Shanta S

Journal of clinical medicine research 20200722 8

Despite high morbidity and mortality of ongoing coronavirus disease 2019 (COVID-19) pandemic, no specific therapy has been established till date. Though <i>in vitro</i> studies identified various molecules as possible therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these findings call for substantiation by human studies. We conducted this review aiming at reporting evidences on therapies used so far globally for management of COVID-19 in clinical settings. We sear ...[more]

PMID: 32849934

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Project description:Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

Project description:The outbreak of a novel coronavirus (SARS-CoV-2) has caused a major public health concern across the globe. SARS-CoV-2 is the seventh coronavirus that is known to cause human disease. As of September 2020, SARS-CoV-2 has been reported in 213 countries and more than 31 million cases have been confirmed, with an estimated mortality rate of ∼3%. Unfortunately, a drug or vaccine is yet to be discovered to treat COVID-19. Thus, repurposing of existing cancer drugs will be a novel approach in treating COVID-19 patients. These drugs target viral replication cycle, viral entry and translocation to the nucleus. Some can enhance innate antiviral immune response as well. Hence this review focuses on comprehensive list of 22 drugs that work against COVID-19 infection. These drugs include fingolimod, colchicine, N4-hydroxycytidine, remdesivir, methylprednisone, oseltamivir, icatibant, perphanizine, viracept, emetine, homoharringtonine, aloxistatin, ribavirin, valrubicin, famotidine, almitrine, amprenavir, hesperidin, biorobin, cromolyn sodium, and antibodies- tocilzumab and sarilumab. Also, we provide a list of 31 drugs that are predicted to function against SARS-CoV-2 infection. In summary, we provide succinct overview of various therapeutic modalities. Among these 53 drugs, based on various clinical trials and literature, remdesivir, nelfinavir, methylpredinosolone, colchicine, famotidine and emetine may be used for COVID-19. SIGNIFICANCE: It is of utmost important priority to develop novel therapies for COVID-19. Since the effect of SARS-CoV-2 is so severe, slowing the spread of diseases will help the health care system, especially the number of visits to Intensive Care Unit (ICU) of any country. Several clinical trials are in works around the globe. Moreover, NCI developed a recent and robust response to COVID-19 pandemic. One of the NCI's goals is to screen cancer related drugs for identification of new therapies for COVID-19. https://www.cancer.gov/news-events/cancer-currents-blog/2020/covid-19-cancer-nci-response?cid=eb_govdel.

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Exploring Repurposing Potential of Existing Drugs in the Management of COVID-19 Epidemic: A Critical Review.

Publications

Exploring Repurposing Potential of Existing Drugs in the Management of COVID-19 Epidemic: A Critical Review.

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