Pharmacological Approaches to the Treatment of COVID-19 Patients

Overview

Journal J Transl Sci

Publisher Open Access Text

Date 2020 Oct 12

PMID 33042589

Authors

Lawrence C Sowers

Lucas S Blanton

Scott C Weaver

Randall J Urban

Charles P Mouton

Affiliations

Soon will be listed here.

Abstract

The current COVID-19 pandemic has presented unprecedented challenges to the world community. No effective therapies or vaccines have yet been established. Upon the basis of homologies to similar coronaviruses, several potential drug targets have been identified and are the focus of both laboratory and clinical investigation. The rationale for several of these drug candidates is presented in this review. Emerging clinical data has revealed that severe COVID-19 disease is associated with heightened inflammatory responses and a procoagulant state, suggesting that patient treatment strategies must extend beyond antiviral agents. Effective approaches to the treatment of vulnerable patients with comorbidities will render COVID-19 substantially more manageable.

References

Gralinski L, Baric R . Molecular pathology of emerging coronavirus infections. J Pathol. 2014; 235(2):185-95. PMC: 4267971. DOI: 10.1002/path.4454. View

Buckner T, Key N . Venous thrombosis in blacks. Circulation. 2012; 125(6):837-9. DOI: 10.1161/CIRCULATIONAHA.111.073098. View

Kobori H, Nishiyama A, Abe Y, Navar L . Enhancement of intrarenal angiotensinogen in Dahl salt-sensitive rats on high salt diet. Hypertension. 2003; 41(3):592-7. PMC: 2572575. DOI: 10.1161/01.HYP.0000056768.03657.B4. View

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y . Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395(10223):507-513. PMC: 7135076. DOI: 10.1016/S0140-6736(20)30211-7. View

Chandramohan G, Bai Y, Norris K, Rodriguez-Iturbe B, Vaziri N . Effects of dietary salt on intrarenal angiotensin system, NAD(P)H oxidase, COX-2, MCP-1 and PAI-1 expressions and NF-kappaB activity in salt-sensitive and -resistant rat kidneys. Am J Nephrol. 2007; 28(1):158-67. DOI: 10.1159/000110021. View

Cao J, Forrest J, Zhang X . A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs. Antiviral Res. 2014; 114:1-10. PMC: 7113785. DOI: 10.1016/j.antiviral.2014.11.010. View

Yamaya M, Shimotai Y, Hatachi Y, Lusamba Kalonji N, Tando Y, Kitajima Y . The serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells. Pulm Pharmacol Ther. 2015; 33:66-74. PMC: 7110702. DOI: 10.1016/j.pupt.2015.07.001. View

Liu L, Wang S, Shao Y, Shi J, Wang W, Chen W . Hydroxychloroquine potentiates the anti-cancer effect of bevacizumab on glioblastoma via the inhibition of autophagy. Biomed Pharmacother. 2019; 118:109339. DOI: 10.1016/j.biopha.2019.109339. View

Weiss S, Navas-Martin S . Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev. 2005; 69(4):635-64. PMC: 1306801. DOI: 10.1128/MMBR.69.4.635-664.2005. View

10.

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G . A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020; 382(19):1787-1799. PMC: 7121492. DOI: 10.1056/NEJMoa2001282. View

11.

Diaz J . Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. J Travel Med. 2020; 27(3). PMC: 7184445. DOI: 10.1093/jtm/taaa041. View

12.

Lin L, Lu L, Cao W, Li T . Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020; 9(1):727-732. PMC: 7170333. DOI: 10.1080/22221751.2020.1746199. View

13.

MacKenzie A . Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med. 1983; 75(1A):40-5. DOI: 10.1016/0002-9343(83)91269-x. View

14.

Liu Y, Du X, Chen J, Jin Y, Peng L, Wang H . Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect. 2020; 81(1):e6-e12. PMC: 7195072. DOI: 10.1016/j.jinf.2020.04.002. View

15.

Huchting J, Vanderlinden E, Van Berwaer R, Meier C, Naesens L . Cell line-dependent activation and antiviral activity of T-1105, the non-fluorinated analogue of T-705 (favipiravir). Antiviral Res. 2019; 167:1-5. DOI: 10.1016/j.antiviral.2019.04.002. View

16.

Halliday B, Wassall R, Lota A, Khalique Z, Gregson J, Newsome S . Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2018; 393(10166):61-73. PMC: 6319251. DOI: 10.1016/S0140-6736(18)32484-X. View

17.

Dong S, Sun J, Mao Z, Wang L, Lu Y, Li J . A guideline for homology modeling of the proteins from newly discovered betacoronavirus, 2019 novel coronavirus (2019-nCoV). J Med Virol. 2020; 92(9):1542-1548. PMC: 7228330. DOI: 10.1002/jmv.25768. View

18.

. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100,000 patients in randomized trials. ACE Inhibitor Myocardial Infarction Collaborative Group. Circulation. 1998; 97(22):2202-12. DOI: 10.1161/01.cir.97.22.2202. View

19.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M . Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30(3):269-271. PMC: 7054408. DOI: 10.1038/s41422-020-0282-0. View

20.

Schouten L, van Kaam A, Kohse F, Veltkamp F, Bos L, de Beer F . Age-dependent differences in pulmonary host responses in ARDS: a prospective observational cohort study. Ann Intensive Care. 2019; 9(1):55. PMC: 6517452. DOI: 10.1186/s13613-019-0529-4. View