Evidence map›Paper›PMID 39936915›Full record

ArticleJournal of virology2025

Amino acid substitutions in NSP6 and NSP13 of SARS-CoV-2 contribute to superior virus growth at low temperatures.

Yuri Furusawa, Maki Kiso, Ryuta Uraki, Yuko Sakai-Tagawa, Hiroyuki Nagai, Michiko Koga, Yukie Kashima, Masayuki Hojo, Noriko Iwamoto, Kiyoko Iwatsuki-Horimoto and 7 more

Abstract read
In one paragraph

Article in Journal of virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Yuri FurusawaThe Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Shinjuku, Tokyo, Japan.ORCID 0000-0002-7489-7303
Maki KisoThe University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center, Shinjuku, Tokyo, Japan.
Ryuta UrakiThe Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Shinjuku, Tokyo, Japan.
Yuko Sakai-TagawaDivision of Virology, Institute of Medical Science, University of Tokyo, Shinjuku, Tokyo, Japan.
Hiroyuki NagaiDepartment of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Shinjuku, Tokyo, Japan.
Michiko KogaDepartment of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Shinjuku, Tokyo, Japan.
Yukie KashimaDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Shinjuku, Tokyo, Japan.
Masayuki HojoDepartment of Respiratory Disease, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.
Noriko IwamotoDisease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.ORCID 0000-0001-5471-7363
Kiyoko Iwatsuki-HorimotoThe University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center, Shinjuku, Tokyo, Japan.ORCID 0000-0002-8266-020X
Norio OhmagariDisease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.
Yutaka SuzukiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Shinjuku, Tokyo, Japan.
Hiroshi YotsuyanagiDepartment of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Shinjuku, Tokyo, Japan.
Peter J HalfmannDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Wataru KamitaniDepartment of Infectious Diseases and Host Defense, Graduate School of Medicine, Gunma University, Gunma, Japan.ORCID 0000-0003-0165-9408
Seiya YamayoshiThe Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Shinjuku, Tokyo, Japan.ORCID 0000-0001-7768-5157
Yoshihiro KawaokaThe Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Shinjuku, Tokyo, Japan.ORCID 0000-0001-5061-8296

Funding

NIAID Centers of Excellence for Influenza Research and Response: Universal Influenza Vaccine Research Activities75N93021C00014 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GARCIA-SASTRE, ADOLFO · 2021 to 2025
$62.6M
Japan Agency for Medical Research and Development (AMED) JP243fa627001Japan Agency for Medical Research and Development (AMED) JP243fa827005Japan Agency for Medical Research and Development (AMED) JP24nf0101632Japan Agency for Medical Research and Development (AMED) JP24wm0125002NIAID NIH HHS 75N93021C00014
6 · The paper itself

Abstract

In general, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates well at 37°C, which is the temperature of the human lower respiratory tract, but it poorly at 30°C‒32°C, which is the temperature of the human upper respiratory tract. The replication efficiency of SARS-CoV-2 in the upper respiratory tract may directly affect its transmissibility. In this study, an XBB.1.5 isolate showed superior replicative ability at 32°C and 30°C, whereas most other Omicron sub-variant isolates showed limited growth. Deep sequencing analysis demonstrated that the frequencies of viruses possessing the NSP6-S163P and NSP13-P238S substitutions increased to more than 97% during propagation of the XBB.1.5 isolate at 32°C but did not reach 55% at 37°C. Reverse genetics revealed that these substitutions contributed to superior virus growth IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates efficiently at 37°C. However, the temperature of the human upper airway is 30°C-32°C. Therefore, the replicative ability of SARS-CoV-2 at low temperatures could influence virus replication in the upper airway and transmissibility. In this study, we assessed the growth of Omicron sub-variants at low temperatures and found that an XBB.1.5 isolate showed increased replicative ability. By deep sequencing analysis and reverse genetics, we found that amino acid changes in NSP6 and NSP13 contribute to the low-temperature growth; these changes improved RNA polymerase activity at low temperatures and enhanced virus replication in the upper airway of hamsters. Although these substitutions alone did not drastically affect virus transmissibility, in combination with other substitutions, they could affect virus replication in humans. Furthermore, since these substitutions enhance virus replication in cultured cells, they could be used to improve the production of inactivated or live attenuated vaccine virus.

Indexed as

Amino Acid SubstitutionSARS-CoV-2Viral Nonstructural ProteinsAnimalsChlorocebus aethiopsCold TemperatureCOVID-19CricetinaeHumansMesocricetusVero CellsVirus ReplicationViral Nonstructural ProteinscoronavirusCOVID-19SARS-CoV-2

Identifiers

PMID39936915
PMCPMC11915790

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.