|
Basic Characteristics of Mutations
|
|
Mutation Site
|
E391G |
|
Mutation Site Sentence
|
The numbers of amino acid changes in the specimens, which were commonly detected through day 37, 43, 48 and 58, were 4 in the S (I101T, D178N, E340K/A, S494P), 4 in the ORF1a (L631I (nsp2:L451L), E1209G (nsp3:E391G), R3012K (nsp4:R249K), L4319F (nsp10:L66F)), 4 in the ORF1b (V783I (nsp12: V792I), R1078C (nsp13:R155C), R1502K (nsp13:R579K), V2287I (nsp15:V236I)), and 1 in the N (S202N) compared with the wild-type virus (day 0) (Table 1 and Supplementary Table 1). |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
NSP3 |
|
Standardized Encoding Gene
|
ORF1a
|
|
Genotype/Subtype
|
- |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
COVID-19
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
- |
|
Location
|
Japan |
|
Literature Information
|
|
PMID
|
38348230
|
|
Title
|
Emergence of SARS-CoV-2 with Dual-Drug Resistant Mutations During a Long-Term Infection in a Kidney Transplant Recipient
|
|
Author
|
Tanino Y,Nishioka K,Yamamoto C,Watanabe Y,Daidoji T,Kawamoto M,Uda S,Kirito S,Nakagawa Y,Kasamatsu Y,Kawahara Y,Sakai Y,Nobori S,Inaba T,Ota B,Fujita N,Hoshino A,Nukui Y,Nakaya T
|
|
Journal
|
Infection and drug resistance
|
|
Journal Info
|
2024 Feb 8;17:531-541
|
|
Abstract
|
INTRODUCTION: Various therapeutic agents are being developed for the treatment of coronavirus disease 2019 (COVID-19). Therefore, it is crucial to accumulate information regarding the features of drug-resistant viruses to these antiviral drugs. METHODS: We investigated the emergence of dual-drug resistance in a kidney transplant recipient who received sotrovimab (from day 0) and remdesivir (RDV) (from day 8 to day 17). We sequenced the whole viral genomes from nasopharyngeal swabs taken on day 0 and seven points after starting treatment (on days 12, 19, 23, 37, 43, 48, and 58). The genetic traits of the wild-type (day 0) and descendant viruses (after day 12) were determined by comparing the genomes with those of a Wuhan strain and the day 0 wild-type strain, respectively. Three viral isolates (from samples collected on days 0, 23, and 37) were investigated for their escape ability and growth kinetics in vitro. RESULTS: The sotrovimab resistant mutation (S:E340K) and the RDV resistant mutation RdRp:V792I (nt: G15814A) emerged within 12 days (day 12) and 11 days (day 19) after the treatment, respectively. The day 23 isolate harboring S:E340K/RdRp:V791I was resistant to both sotrovimab and RDV, showing 364- and 2.73-fold higher resistance respectively, compared with the wild-type. Moreover, compared with the day 23 isolate, the day 37 isolate accumulated multiple additional mutations and had a higher level of resistance to both drugs. CONCLUSION: Drug-resistant variants with double mutations (S:E340K/RdRp:V791I) became dominant within 23 days after starting treatment, suggesting that even a combination therapy involving sotrovimab and RDV, dual-drug resistant viruses may emerge rapidly in immunocompromised patients. The dual-resistant variants had lower virus yields than those of the wild-type virus in vitro, suggesting that they paid a fitness cost.
|
|
Sequence Data
|
-
|
|
|