Volume 30, Number 6—June 2024
Research Letter
Sporadic Occurrence of Ensitrelvir-Resistant SARS-CoV-2, Japan
Table
Number of mutations in NSP5 causing ensitrelvir resistance during March 31–December 31, 2023, in study of sporadic occurrence of ensitrelvir-resistant SARS-CoV-2, Japan*
Amino acid substitutions‡ | No. cases from GISAID database† |
|||||
---|---|---|---|---|---|---|
Globally | Japan | China | United States | Europe | Others | |
T45I | 25 | 0 | 1 | 4 | 15 (60.0) | 5 |
D48Y | 0 | 0 | 0 | 0 | 0 | 0 |
M49I | 90 | 6 | 0 | 77 (85.6) | 5 | 2 |
M49L | 277 | 256 (92.4) | 2 | 15 | 0 | 4 |
M49T | 1 | 0 | 0 | 0 | 0 | 1 |
M49V | 1 | 0 | 0 | 1 | 0 | 0 |
L50F | 85 | 6 | 2 | 31 | 26 | 20 |
P52L | 4 | 2 | 0 | 0 | 0 | 2 |
Y54C | 0 | 0 | 0 | 0 | 0 | 0 |
S144A | 4 | 2 | 0 | 0 | 1 | 1 |
E166A | 1 | 1 | 0 | 0 | 0 | 0 |
E166V | 23 | 0 | 1 | 4 | 10 | 8 |
L167F | 0 | 0 | 0 | 0 | 0 | 0 |
P168del | 4 | 0 | 0 | 0 | 0 | 4 |
A173T | 23 | 0 | 1 | 6 | 11 | 5 |
A173V | 23 | 2 | 0 | 6 | 3 | 12 (52.2) |
Q192R | 2 | 0 | 0 | 0 | 1 | 1 |
*Numbers in parentheses are percentages of total global cases (if a particular mutation was found in >10 cases and was responsible for >50% of global cases). del, deletion; NSP5, nonstructural protein 5. †Sequences were extracted from the GISAID EpiCoV database (https://www.gisaid.org). ‡Amino acid substitutions in NSP5 that trigger emergence of ensitrelvir-resistant SARS-CoV-2 (5–8).
References
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103004 . DOIPubMedGoogle Scholar - Japan Ministry of Health. Labour and Welfare. Usage of drugs for the treatment of novel coronavirus infections [cited 2023 Dec 31]. https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000121431_00324.html
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eade8778 . DOIPubMedGoogle Scholar - Jochmans D, Liu C, Donckers K, Stoycheva A, Boland S, Stevens SK, et al. The substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro are selected by a protease inhibitor in vitro and confer resistance to nirmatrelvir. MBio. 2023;14:
e0281522 . DOIPubMedGoogle Scholar - Doi A, Tomita Y, Okura H, Matsuyama S. Frequent occurrence of mutations in nsp3 and nsp4 of SARS-CoV-2, presumably caused by the inhaled asthma drug ciclesonide. PNAS Nexus. 2022;1:pgac197.
- Japan National Institute of Infectious Diseases. Amino acid substitutions due to viral genomic mutations that may affect the efficacy of therapeutic drugs against the new coronavirus (SARS-CoV-2) (4th edition) [cited 2023 Dec 31]. https://www.niid.go.jp/niid/ja/2019-ncov/2624-flu/12170-sars-cov-2-mutation-v4.html
1Current affiliation: ACEL Inc., Kanagawa, Japan.