Masaaki Nakashima , Haruaki Nobori , Takayuki Kuroda , Alice Shimba , Satoshi Miyagawa , Akane Hayashi , Kazumi Matsumoto , Mei Yoshida , Kaoru Baba , Teruhisa Kato , Keita Fukao
{"title":"口服 3CL 蛋白酶抑制剂 ensitrelvir 可抑制仓鼠气溶胶传播模型中 SARS-CoV-2 的脱落和感染。","authors":"Masaaki Nakashima , Haruaki Nobori , Takayuki Kuroda , Alice Shimba , Satoshi Miyagawa , Akane Hayashi , Kazumi Matsumoto , Mei Yoshida , Kaoru Baba , Teruhisa Kato , Keita Fukao","doi":"10.1016/j.antiviral.2024.106026","DOIUrl":null,"url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) remain a major global health challenge, with aerosol transmission being the primary route of spread. The use of antivirals as medical countermeasures to control SARS-CoV-2 transmission and spread is promising but remains to be clarified. The current study established and used an <em>in vivo</em> hamster aerosol transmission model system to evaluate the efficacy of the protease inhibitor ensitrelvir to prevent the spread of SARS-CoV-2. Male Index Syrian hamsters were intranasally infected with SARS-CoV-2, paired with naïve Contact hamsters, and co-housed for 12 h under conditions to allow for only aerosol transmission. The Index hamsters were treated three times with ensitrelvir starting 8 h post infection, or the Contact hamsters were treated once with ensitrelvir 12 h prior to co-housing. Viral infection and transmission were monitored by evaluating nasal lavage fluid, lung tissues, and body and lung weights. Post-infection administration of ensitrelvir to Index hamsters suppressed virus shedding in a dose-dependent manner. Pre-exposure administration of 750 mg/kg ensitrelvir to naïve Contact hamsters also protected against aerosol SARS-CoV-2 infection in a dose-dependent manner. Furthermore, pre-exposure treatment of 750 mg/kg ensitrelvir supressed body weight loss and lung weight increase of aerosol infected hamsters compared to vehicle-treated hamsters. These findings suggest that ensitrelvir may prevent SARS-CoV-2 spread when administered to infected patients and may prevent or limit SARS-CoV-2 infection when prophylactically administered to non-infected individuals. Both approaches may help protect at-risk individuals, such as family members living with SARS-CoV-2-infected patients.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oral 3CL protease inhibitor ensitrelvir suppressed SARS-CoV-2 shedding and infection in a hamster aerosol transmission model\",\"authors\":\"Masaaki Nakashima , Haruaki Nobori , Takayuki Kuroda , Alice Shimba , Satoshi Miyagawa , Akane Hayashi , Kazumi Matsumoto , Mei Yoshida , Kaoru Baba , Teruhisa Kato , Keita Fukao\",\"doi\":\"10.1016/j.antiviral.2024.106026\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) remain a major global health challenge, with aerosol transmission being the primary route of spread. The use of antivirals as medical countermeasures to control SARS-CoV-2 transmission and spread is promising but remains to be clarified. The current study established and used an <em>in vivo</em> hamster aerosol transmission model system to evaluate the efficacy of the protease inhibitor ensitrelvir to prevent the spread of SARS-CoV-2. Male Index Syrian hamsters were intranasally infected with SARS-CoV-2, paired with naïve Contact hamsters, and co-housed for 12 h under conditions to allow for only aerosol transmission. The Index hamsters were treated three times with ensitrelvir starting 8 h post infection, or the Contact hamsters were treated once with ensitrelvir 12 h prior to co-housing. Viral infection and transmission were monitored by evaluating nasal lavage fluid, lung tissues, and body and lung weights. Post-infection administration of ensitrelvir to Index hamsters suppressed virus shedding in a dose-dependent manner. Pre-exposure administration of 750 mg/kg ensitrelvir to naïve Contact hamsters also protected against aerosol SARS-CoV-2 infection in a dose-dependent manner. Furthermore, pre-exposure treatment of 750 mg/kg ensitrelvir supressed body weight loss and lung weight increase of aerosol infected hamsters compared to vehicle-treated hamsters. These findings suggest that ensitrelvir may prevent SARS-CoV-2 spread when administered to infected patients and may prevent or limit SARS-CoV-2 infection when prophylactically administered to non-infected individuals. Both approaches may help protect at-risk individuals, such as family members living with SARS-CoV-2-infected patients.</div></div>\",\"PeriodicalId\":8259,\"journal\":{\"name\":\"Antiviral research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antiviral research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0166354224002377\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antiviral research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0166354224002377","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Oral 3CL protease inhibitor ensitrelvir suppressed SARS-CoV-2 shedding and infection in a hamster aerosol transmission model
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) remain a major global health challenge, with aerosol transmission being the primary route of spread. The use of antivirals as medical countermeasures to control SARS-CoV-2 transmission and spread is promising but remains to be clarified. The current study established and used an in vivo hamster aerosol transmission model system to evaluate the efficacy of the protease inhibitor ensitrelvir to prevent the spread of SARS-CoV-2. Male Index Syrian hamsters were intranasally infected with SARS-CoV-2, paired with naïve Contact hamsters, and co-housed for 12 h under conditions to allow for only aerosol transmission. The Index hamsters were treated three times with ensitrelvir starting 8 h post infection, or the Contact hamsters were treated once with ensitrelvir 12 h prior to co-housing. Viral infection and transmission were monitored by evaluating nasal lavage fluid, lung tissues, and body and lung weights. Post-infection administration of ensitrelvir to Index hamsters suppressed virus shedding in a dose-dependent manner. Pre-exposure administration of 750 mg/kg ensitrelvir to naïve Contact hamsters also protected against aerosol SARS-CoV-2 infection in a dose-dependent manner. Furthermore, pre-exposure treatment of 750 mg/kg ensitrelvir supressed body weight loss and lung weight increase of aerosol infected hamsters compared to vehicle-treated hamsters. These findings suggest that ensitrelvir may prevent SARS-CoV-2 spread when administered to infected patients and may prevent or limit SARS-CoV-2 infection when prophylactically administered to non-infected individuals. Both approaches may help protect at-risk individuals, such as family members living with SARS-CoV-2-infected patients.
期刊介绍:
Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.