Scientific Online Resource System

Annual for Hospital Pharmacy

Remdesivir—the medicine that has proven to be a successful new health technology in the battle against COVID-19

Orlin Nedev, Evgeni Grigorov

Abstract

The global COVID-19 pandemic caused by the viral pathogen SARS-CoV-2 has surged the biomedical community into action to discover and develop effective antiviral drugs. One potential therapeutic approach currently being evaluated in multiple clinical trials is the medicinal product—remdesivir, which has had a tortuous development path over the past eight years. In essence, it is a nucleotide analog prodrug that inhibits viral replication. It was initially evaluated in clinical trials to prevent the Ebola outbreak in 2014. Subsequent evaluation by multiple virology laboratories around the world demonstrated remdesivir's ability to inhibit coronavirus replication, including the SARS-CoV-2 virus which is the cause of the current pandemic. In the presented paper, the authors provide an overview of the discovery of remdesivir, its mechanism of action, and current studies investigating its clinical effectiveness.


Keywords

remdesivir, COVID-19, pandemic, medicament

Full Text


References

• Веков, Т., П. Салчев, С. Джамбазов, П. Димитров. Добри практики за оценка на здравни технологии, БКИ, София, 2019г

• Веков, Т., Е. Григоров, Н. Велева, С. Джамбазов, Оценки на лекарствени терапии. Теория и практика, Учебник, МУ - Плевен 2015 г..

• Гетов, И., Е. Насева, Х. Лебанова, Е. Григоров, Фармакоепидемиология, Учебник, Екопринт, С.2013г.

• Димитров, П., Джамбазов С., Салчев П., Веков Т., Меков Е., Славчев Г. Практическа епидемиология. ЦМБ, София, 2019г.

• Салчев, П., Веков Т., Джамбазов С., Димитров П. Социална медицина, БКИ, София, 2020г.

• Anderson, R.M., C. Fraserm, A.C. Ghanim, C.A. Donnelly, S. Riley, N.M. Ferguson, G.M. Leung, T.H. Lam, A.J. Hedley. (2004) Epidemiology, transmission dynamics and control of SARS: The 2002-2003 epidemic. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 359: 1091–1105.

• Azhar, E.I., D.S.C. Hui, Z.A. Memish, C. Drosten, A. Zumla. (2019) The Middle East respiratory syndrome (MERS). Infectious Disease Clinics of North America 33: 891–905.

• Bao, L., W. Deng, B. Huang, H. Gao, J. Liu, L. Ren, Q. Wei, P. Yu, Y. Xu, F. Qi, et al. (2020) The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature. 583:830–83.

• Bassetto, F., P. Marchica, G.P. Azzena, T. Brambullo, F. Facchin, G. Masciopinto, L. Pandis, and V. Vindigni. (2021) Brief history in the time of SARS-CoV-2 pandemic in Italy. A close look on a plastic surgery unit and plastic surgeons efforts during the COVID-19 outbreak. Annali Italiani di Chirurgia. 10:S0003469X21034886.

• Bixler, S.L., A.J. Duplantier, S. Bavari. (2017) Discovering drugs for the treatment of Ebola virus. Current Treatment Options in Infectious Diseases. 9:299–317.

• Blower, S., D. Bernoulli. (2004) An attempt at a new analysis of the mortality caused by smallpox and of the advantages of inoculation to prevent it. Reviews in Medical Virology. 14:275–288.

• Chenoweth, A.M., B.D. Wines, J.C. Anania, P. Mark-Hogarth. )2020) Harnessing the immune system via FcγR function in immune therapy: A pathway to next-gen mAbs. Immunology and Cell Biology. 98:287–304.

• de Cock, K.M., H.W. Jaffe, J.W. Curran. (2021) Reflections on 40 years of AIDS. Emerging Infectious Diseases. 27:1553–1560.

• Dicken, S.J., Murray, M.J., Thorne, L.G., Reuschl, A.K., Forrest, C., Ganeshalingham, M., Muir, L., Kalemera, M.D., Palor, M., McCoy, L.E et al. (2021) Characterisation of B.1.1.7 and pangolin coronavirus spike provides insights on the evolutionary trajectory of SARS-CoV-2. bioRxiv. 03.22.436468.

• Eastman, R.T., J.S. Roth, K.R. Brimacombe, A. Simeonov, M. Shen, S. Patnaik, M.D. Hall. (2020) Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19. ACS Central Science. 6: 672–683.

• GBD. HIV collaborators. (2017) Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: A systematic analysis for the global burden of diseases, injuries, and risk factors study 2017. Lancet HIV. 6: e831–ee59.

• Gilead Sciences Initiates Two Phase 3 Studies of Investigational Antiviral Remdesivir for the Treatment of COVID-19, U.S. FDA Grants Investigational New Drug Authorization to Study Remdesivir for the Treatment of COVID-19, 2020.

• Glatter, K.A., P. Finkelman. (2021) History of the plague: An ancient pandemic for the age of COVID-19. The American Journal of Medicine. 134:176–181.

• Gurwitz, D. (2020) Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Development Research. 81:537–540.

• Hoenen, T., A. Groseth, H. Feldmann. (2019) Therapeutic strategies to target the Ebola virus life cycle. Nature Reviews. Microbiology. 17:593–606.

• Hui, D.S.C., A. Zumla. (2019) Severe acute respiratory syndrome: Historical, epidemiologic, and clinical features. Infectious Disease Clinics of North America. 33:869–889.

• Jean, S.S., P.I. Lee, P.R. Hsueh. (2020) Treatment options for COVID-19: The reality and challenges. Journal of Microbiology, Immunology, and Infection. 53:436–443.

• Jester, B., T. Uyeki, D. Jernigan. (2018) Readiness for responding to a severe pandemic 100 years after 1918. American Journal of Epidemiology. 187:2596–2602.

• Jester, B.J., T.M. Uyeki, D.B. Jernigan. (2020) Fifty years of influenza a(H3N2) following the pandemic of 1968. American Journal of Public Health. 110:669–676.

• Johns Hopkins University Coronavirus Resource Center, (2021). https://coronavirus.jhu.edu/.

• Johnson, N.P., J. Mueller. (2002) Updating the accounts: Global mortality of the 1918-1920 “Spanish” influenza pandemic. Bulletin of the History of Medicine. 76:105–115.

• Jordheim, L.P., D. Durantel, F. Zoulim, C. Dumontet. (2013) Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nature Reviews. Drug Discovery. 12:447–464.

• Krylova, O., D.J.D. Earn. (2020) Patterns of smallpox mortality in London, England, over three centuries. PLoS Biology. 18:e3000506.

• Labbé, M.O., L. Collins, C.A. Lefebvre, W. Maharsy, J. Beauregard, S. Dostie, M. Prévost, M. Nemer, Y. Guindon. (2020) Identification of a C3’-nitrile nucleoside analogue inhibitor of pancreatic cancer cell line growth. Bioorganic & Medicinal Chemistry Letters. 30:126983.

• Linka, K., M. Peirlinck, E. Kuhl. (2020) The reproduction number of COVID-19 and its correlation with public health interventions. Computational Mechanics. 28:1–16.

• Liu, Y., A.A. Gayle, A. Wilder-Smith, J. Rocklöv. (2020) The reproductive number of COVID-19 is higher compared to SARS coronavirus. Journal of Travel Medicine. 27:taaa021.

• Liya, G., W. Yuguang, L. Jian, Y. Huaiping, H. Xue, H. Jianwei, M. Jiaju, L. Youran, M. Chen, J. Yiqing. (2020) Studies on viral pneumonia related to novel coronavirus SARS-CoV-2, SARS-CoV, and MERS-CoV: A literature review. APMIS. 128:423–432.

• Malin, J.J., I. Suárez, V. Priesner, G. Fätkenheuer, and J. Rybniker. (2020) Remdesivir against COVID-19 and other viral diseases. Clinical Microbiology Reviews. 34:e00162–e00120.

• Ottoni, M.P., J.D. Ricciardone, A. Nadimpalli, S. Singh, A.M. Katsomya, L.M. Pokoso, R. Petrucci. (2020) Ebola-negative neonates born to Ebola-infected mothers after monoclonal antibody therapy: A case series. The Lancet Child & Adolescent Health. 4:884–888.

• Pruijssers, A.J., A.S. George, A. Schäfer, S.R. Leist, L.E. Gralinksi, K.H. Dinnon 3rd., B.L. Yount, M.L. Agostini, L.J. Stevens, J.D. Chappell, et al. (2020) Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice. Cell Reports. 32:107940.

• Rabaan, A.A., S.H. Al-Ahmed, S. Haque, R. Sah, R. Tiwari, Y.S. Malik, K. Dhama, M.I. Yatoo, D.K. Bonilla-Aldana, A.J. Rodriguez-Morales. (2020) SARS-CoV-2, SARS-CoV, and MERS-COV: A comparative overview. Le Infezioni in Medicina. 28:174–184.

• Reynolds, P., and A. Marzi. 2017. Ebola and Marburg virus vaccines. Virus Genes 53: 501–515.

• Ruchelman, A.L., H.W. Man, R. Chen, W. Liu, L. Lu, D. Cedzik, L. Zhang, J. Leisten, A. Collette, R.K. Narla, et al. (2011) 1,1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4. Bioorganic & Medicinal Chemistry. 19:6356–6374.

• Salzberger, B., A. Mohr, and F. Hitzenbichler. 2018. Die influenza 1918 [the pandemic influenza 1918]. Deutsche Medizinische Wochenschrift. 143:1858–1863.

• Santander-Ballestín, S., D. Gómez-Martín, S. Lorente-Pérez, M.J. Luesma-Bartolomé. (2021) Hepatitis C: A pharmacological therapeutic update. Journal of Clinical Medicine 10: 1568.

• Satarker, S., M. Nampoothiri. (2020) Structural proteins in severe acute respiratory syndrome coronavirus-2. Archives of Medical Research. 51:482–491.

• Shen, Y., W. Eades, B. Yan. (2021) The COVID-19 medicine remdesivir is activated by carboxylesterase-1 and excessive hydrolysis increases cytotoxicity. Hepatology Communications. 5(9):1622-23.

• Shen, Y., W. Eades, B. Yan. (2021) Remdesivir potently inhibits carboxylesterase-2 through covalent modifications: Signifying strong drug-drug interactions. Fundamental & Clinical Pharmacology. 35:432–434.

• Shifflett, K., A. Marzi. (2019) Marburg virus pathogenesis - differences and similarities in humans and animal models. Virology Journal. 16:165.

• Singh, A.K., A. Singh, R. Singh, A. Misra. (2020) Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies. Diabetes and Metabolic Syndrome: Clinical Research and Reviews. 14:641–648.

• Song, Y., M. Zhang, L. Yin, K. Wang, Y. Zhou, M. Zhou, Y. Lu. (2020) COVID-19 treatment: Close to a cure? A rapid review of pharmacotherapies for the novel coronavirus (SARS-CoV-2). International Journal of Antimicrobial Agents. 56:106080.

• Staniland, K., G. Smith. (2013) Flu frames. Sociology of Health & Illnes. 35:309–324.

• Tabish, S.A. (2020) COVID-19 pandemic: Emerging perspectives and future trends. Journal of Public Health Research. 9:1786.

• Tao, X., Y. Lu, Y. Zhou, L. Zhang, Y. Chen. (2020) Efficacy and safety of the regimens containing tenofovir alafenamide versus tenofovir disoproxil fumarate in fixed-dose single-tablet regimens for initial treatment of HIV-1 infection: A meta-analysis of randomized controlled trials. International Journal of Infectious Diseases. 93:108–117.

• Tchesnokov, E.P., J.Y. Feng, D.P. Porter, M. Götte. (2019) Mechanism of inhibition of Ebola virus RNA-dependent RNA polymerase by Remdesivir. Viruses. 11:326.

• Tretyakova, E.V., E.V. Salimova, L.V. Parfenova, M.M. Yunusbaeva, L.U. Dzhemileva, V.A. D'yakonov, U.M. Dzhemilev. (2019) Synthesis of new dihydroquinopimaric acid analogs with nitrile groups as apoptosis-inducing anticancer agents. Anti-Cancer Agents in Medicinal Chemistry. 19:1172–1183.

• Warren, T.K., R. Jordan, M.K. Lo, A.S. Ray, R.L. Mackman, V. Soloveva, D. Siegel, M. Perron, R. Bannister, H.C. Hui, et al. (2016) Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 531:381–385.

• Yao, X., F. Ye, M. Zhang, C. Cui, B. Huang, P. Niu, X. Liu, L. Zhao, E. Dong, C. Song, et al. (2020) In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical Infectious Diseases. 71:732–739.

• Yin, W., C. Mao, X. Luan, D.D. Shen, Q. Shen, H. Su, X. Wang, F. Zhou, W. Zhao, M. Gao, et al. (2020) Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science. 368:1499–1504.




DOI: http://dx.doi.org/10.14748/ahp.v8i1.8616

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