SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801.
Nature
; 591(7850): 451-457, 2021 03.
Article
in English
| MEDLINE | ID: covidwho-1075231
ABSTRACT
All coronaviruses known to have recently emerged as human pathogens probably originated in bats1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801-an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials-markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Cytidine
/
COVID-19
/
COVID-19 Drug Treatment
/
Hydroxylamines
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Nature
Year:
2021
Document Type:
Article
Affiliation country:
S41586-021-03312-w
Similar
MEDLINE
...
LILACS
LIS