A Comprehensive Review of Paxlovid: Composition, Mechanism, Clinical Research, and Adverse Reactions in the Treatment of COVID-19
Keywords:
COVID-19, SARS-CoV-2, Paxlovid treatment, Adverse reactionsAbstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an unprecedented public health crisis. Paxlovid, a small molecule oral drug produced by Pfizer, has been licensed in several countries and territories for the treatment of COVID-19. Due to its short time to market, clinical research on Paxlovid is still ongoing and is a hot spot in medical and pharmaceutical research. This article reviews the latest research on Paxlovid within about one year after its launch from the aspects of its composition and structure, mechanism of action, clinical research, and adverse reactions. It aims to enable clinicians to use Paxlovid more reasonably in the process of daily treatment and management of patients, and provide more research directions for researchers on Paxlovid.
References
[1]Habas K, Nganwuchu C, Shahzad F, Gopalan R, Haque M, Rahman S, Majumder AA, Nasim T. Resolution of coronavirus disease 2019 (COVID-19). Expert Rev Anti Infect Ther. 2020 Dec;18(12):1201-1211. doi: 10.1080/14787210.2020.1797487. Epub 2020 Aug 4. PMID: 32749914.
[2]Ren SY, Wang WB, Gao RD, Zhou AM. Omicron variant (B.1.1.529) of SARS-CoV-2: Mutation, infectivity, transmission, and vaccine resistance. World J Clin Cases. 2022 Jan 7;10(1):1-11. doi: 10.12998/wjcc.v10.i1.1. PMID: 35071500; PMCID: PMC8727245.
[3]FDA. Fact sheet for health care providers: Emergency Use Authorization for Paxlovid. December 22, 2021. Available at: https://bit.ly/3sTNGqh. Accessed January 6, 2022.
[4]Zhang, M. (2022, February 14). Pfizer's COVID-19 Oral Medication Obtains Emergency Approval in China, and Related Concept Stocks Have Soared in Advance. Securities Daily, B02. https://doi.org/10.28096/n.cnki.ncjrb.2022.000603
[5]Reina J, Iglesias C. Nirmatrelvir más ritonavir (Paxlovid) una potente combinación inhibidora de la proteasa 3CLpro del SARS-CoV-2 [Nirmatrelvir plus ritonavir (Paxlovid) a potent SARS-CoV-2 3CLpro protease inhibitor combination]. Rev Esp Quimioter. 2022 Jun;35(3):236-240. Spanish. doi: 10.37201/req/002.2022. Epub 2022 Feb 21. PMID: 35183067; PMCID: PMC9134883.
[6]Murugan NA, Raja KMP, Saraswathi NT. Peptide-Based Antiviral Drugs. Adv Exp Med Biol. 2021;1322:261-284. doi: 10.1007/978-981-16-0267-2_10. PMID: 34258744.
[7]Rubin R. From Positive to Negative to Positive Again-The Mystery of Why COVID-19 Rebounds in Some Patients Who Take Paxlovid. JAMA. 2022 Jun 28;327(24):2380-2382. doi: 10.1001/jama.2022.9925. PMID: 35675094.
[8]National Center for Biotechnology Information. PubChem Compound Summary for CID 155903259, Nirmatrelvir. https://pubchem.ncbi.nlm.nih.gov/compound/Nirmatrelvir. Accessed Jan. 13, 2023.
[9]National Center for Biotechnology Information. PubChem Compound Summary for CID 392622, Ritonavir. https://pubchem.ncbi.nlm.nih.gov/compound/Ritonavir. Accessed Jan. 13, 2023.
[10]C. Wang, P. W. Horby, F. G. Hayden, and G. F. Gao, “A novel coronavirus outbreak of global health concern,” The Lancet, vol. 395, no. 10223, pp. 470–473, 2020.
[11]J. Ziebuhr, “Molecular biology of severe acute respiratory syndrome coronavirus,” Current Opinion in Microbiology, vol. 7, no. 4, pp. 412–419, 2004.
[12]Marzi M, Vakil MK, Bahmanyar M, Zarenezhad E. Paxlovid: Mechanism of Action, Synthesis, and In Silico Study. Biomed Res Int. 2022 Jul 7;2022:7341493. doi: 10.1155/2022/7341493. PMID: 35845944; PMCID: PMC9283023.
[13]Hammond J, Leister-T ebbe H, Gardner A, et al. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med 2022;386:1397-408.
[14]Lemaitre F, Grégoire M, Monchaud C, Bouchet S, Saint-Salvi B, Polard E; SFPT Therapeutic Drug Monitoring and Treatment Personalization group (STP-PT) of the French Society of Pharmacology and Therapeutics (SFPT); French Pharmacovigilance Network (CRPV); ANRS-MIE AC-43 Clinical Pharmacology Committee, joint working group; SFPT Therapeutic Drug Monitoring and Treatment Personalization group (STP-PT) of the French Society of Pharmacology and Therapeutics (SFPT); French Pharmacovigilance Network (CRPV); ANRS-MIE AC-43 Clinical Pharmacology Committee, joint working group. Management of drug-drug interactions with nirmatrelvir/ritonavir in patients treated for Covid-19: Guidelines from the French Society of Pharmacology and Therapeutics (SFPT). Therapie. 2022 Sep-Oct;77(5):509-521. doi: 10.1016/j.therap.2022.03.005. Epub 2022 Apr 20. PMID: 35618549; PMCID: PMC9020499.
[15]Yan G, Zhou J, Zhu H, Chen Y, Lu Y, Zhang T, Yu H, Wang L, Xu H, Wang Z, Zhou W. The feasibility, safety, and efficacy of Paxlovid treatment in SARS-CoV-2-infected children aged 6-14 years: a cohort study. Ann Transl Med. 2022 Jun;10(11):619. doi: 10.21037/atm-22-2791. PMID: 35813342; PMCID: PMC9263777.
[16]Shen Y , Ai J, Lin N, Zhang H, Li Y , Wang H, et al. An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 Omicron variants. Emerg Microb Infect. (2022) 11:1518–23. doi: 10.1080/22221751.2022.2078230
[17]Papathanasiou J, Kashilska Y , Bozov H, Petrov I, Masiero S. The outbreak of the SARS-CoV-2 Omicron variant make imperative the adoption of telerehabilitation in the Bulgarian health care system. Eur J Trans Myol. (2022) 32:10355. doi: 10.4081/ejtm.2022.10355
[18]Christensen PA, Olsen RJ, Long SW, Snehal R, Davis JJ, Ojeda Saavedra M, et al. Signals of significantly increased vaccine breakthrough, decreased hospitalization rates, and less severe disease in patients with coronavirus disease 2019 caused by the Omicron variant of severe acute respiratory syndrome coronavirus 2 in Houston, Texas. Am J Pathol. (2022) 192:642–52. doi: 10.1016/ j.ajpath.2022.01.007
[19]Dejnirattisai W, Huo J, Zhou D, Zahradník J, Supasa P , Liu C, et al. SARSCoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Cell. (2022) 185:467–84.e15.
[20]Carreño JM, Alshammary H, Tcheou J, Singh G, Raskin AJ, Kawabata H, et al.Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature.(2022) 602:682–8. doi: 10.1038/d41586-021-03846-z
[21]Zhong W, Jiang X, Yang X, Feng T, Duan Z, Wang W, Sun Z, Chen L, Nie X, Zhu C, Zhang W, Li Y. The efficacy of paxlovid in elderly patients infected with SARS-CoV-2 omicron variants: Results of a non-randomized clinical trial. Front Med (Lausanne). 2022 Sep 6;9:980002. doi: 10.3389/fmed.2022.980002. PMID: 36148451; PMCID: PMC9485497.
[22]Devresse A, Sébastien Briol, De Greef J, Lemaitre F, Boland L, Haufroid V, Scohy A, Kabamba B, Yombi JC, Belkhir L, Darius T, Buemi A, De Potter K, Mantegazza R, Bearzatto B, Goffin E, Kanaan N. Safety, Efficacy, and Relapse of Nirmatrelvir-Ritonavir in Kidney Transplant Recipients Infected With SARS-CoV-2. Kidney Int Rep. 2022 Nov;7(11):2356-2363. doi: 10.1016/j.ekir.2022.08.026. Epub 2022 Aug 28. PMID: 36060621; PMCID: PMC9420244.
[23]DL Heymann, N Shindo WHO Scientific and Technical Advisory Group for Infectious Hazards. COVID-19: what is next for public health Lancet, 395 (10224) (2020), pp. 542-545, 10.1016/S0140-6736(20)30374-3 Epub 2020 Feb 13. PMID:32061313; PMCID: PMC7138015
[24]Cai H, Yan J, Wang J, Che X, Mou S. Efficacy of Paxlovid in patients with acute kidney injury who developed COVID-19. J Infect. 2022 Dec;85(6):702-769. doi: 10.1016/j.jinf.2022.10.002. Epub 2022 Oct 8. PMID: 36220502; PMCID: PMC9546778.
[25]FDA. Fact Sheet For Healthcare Providers: Emergency Use Authorization For Paxlovid. FDA. 2022. www.fda.gov. Accessed 30 Dec 2021.
[26]Kong K, Chang Y, Qiao H, Zhao C, Chen X, Rong K, Zhang P, Jin M, Zhang J, Li H, Zhai Z. Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis. J Transl Med. 2022 Nov 26;20(1):549. doi: 10.1186/s12967-022-03770-4. PMID: 36435786; PMCID: PMC9701426.
[27]Hu Y, Lewandowski EM, Tan H, Zhang X, Morgan RT, Zhang X, Jacobs LMC, Butler SG, Gongora MV, Choy J, Deng X, Chen Y, Wang J. Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir. bioRxiv [Preprint]. 2022 Sep 6:2022.06.28.497978. doi: 10.1101/2022.06.28.497978. PMID: 36119652; PMCID: PMC9479041.
[28]Inhibitors and inducers of CYP enzymes, P-glycoprotein, and other transporters. Med Lett Drugs Ther 2021 October 20 (epub).
[29]Rubin R. From Positive to Negative to Positive Again-The Mystery of Why COVID-19 Rebounds in Some Patients Who Take Paxlovid. JAMA. 2022 Jun 28;327(24):2380-2382. doi: 10.1001/jama.2022.9925. PMID: 35675094.
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