Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection

Wujun Chen; Bing Liang; Xiaolin Wu; Ling Li; Chao Wang; Dongming Xing

doi:10.1016/j.jpha.2022.10.005

Volume 13 Issue 3

Mar. 2023

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Wujun Chen, Bing Liang, Xiaolin Wu, Ling Li, Chao Wang, Dongming Xing. Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection[J]. Journal of Pharmaceutical Analysis, 2023, 13(3): 255-261. doi: 10.1016/j.jpha.2022.10.005

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Wujun Chen, Bing Liang, Xiaolin Wu, Ling Li, Chao Wang, Dongming Xing. Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection[J]. Journal of Pharmaceutical Analysis, 2023, 13(3): 255-261. doi: 10.1016/j.jpha.2022.10.005

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Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection

doi: 10.1016/j.jpha.2022.10.005

Wujun Chen^a,b,
Bing Liang^a,b,
Xiaolin Wu^a,b,
Ling Li^c,
Chao Wang^{a,b
,
,},
Dongming Xing^{a,b,d
,
,}

a. Cancer Institute; Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266071, China;
b. Qingdao Cancer Institute, Qingdao University, Qingdao, Shandong, 266071, China;
c. Department of Pharmacy, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, 519000, China;
d. School of Life Sciences, Tsinghua University, Beijing, 100084, China

Funds:

This study was supported by the Qingdao Major Scientific and Technological Project for Distinguished Scholars (Project No.: 20170103), the Laoshan Major Scientific and Technological Project for Distinguished Scholars (Project No.: 20181030), the Natural Science Foundation of Shandong Province (Project No.: ZR2020MH369), the Hospital Pharmacy Research Foundation of Guangdong Province (Project No.: 2022A01), and the Science and Technology Planning Project in Zhuhai (Project No.: ZH2202200090HJL).

Received Date: Jun. 16, 2022
Accepted Date: Oct. 29, 2022
Rev Recd Date: Oct. 27, 2022
Publish Date: Nov. 02, 2022

Abstract

Abstract

On December 22, 2021, the United States Food and Drug Administration approved the first main protease inhibitor, i.e., oral antiviral nirmatrelvir (PF-07321332)/ritonavir (Paxlovid), for the treatment of early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nirmatrelvir inhibits SARS-CoV-2 infection, but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression. The chiral structure of nirmatrelvir plays a key role in its antiviral activity. Ritonavir boosts the efficacy of nirmatrelvir by inactivating cytochrome P450 3A4 expression and occupying the plasma protein binding sites. Multidrug resistance protein 1 inhibitors may increase the efficacy of nirmatrelvir. However, Paxlovid has many contraindications. Some patients treated with Paxlovid experience a second round of coronavirus disease 2019 (COVID-19) symptoms soon after recovery. Interestingly, the antiviral activity of nirmatrelvir metabolites, such as compounds 12–18 , is similar to or higher than that of nirmatrelvir. Herein, we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge for drug developers and physicians in the fight against COVID-19.
- Nirmatrelvir,
- Pharmacology,
- Pharmacokinetics,
- Toxicology,
- Derivatives,
- COVID-19

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References(69)

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