Coronaviruses Lacking Exoribonuclease Activity Are Susceptible to Lethal Mutagenesis: Evidence for Proofreading and Potential Therapeutics
TLDR
ExoN is identified as the first viral protein distinct from the RdRp that determines the sensitivity of RNA viruses to mutagens, and shows the importance of ExoN as a target for inhibition, and suggests that small-molecule inhibitors of ExON activity could be potential pan-CoV therapeutics in combination with RBV or RNA mutagen.Citations
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Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus.
Bette T. Korber,Will Fischer,Sandrasegaram Gnanakaran,Hyejin Yoon,James Theiler,Werner Abfalterer,Nick Hengartner,Elena E. Giorgi,Tanmoy Bhattacharya,Brian T. Foley,Kathryn M. Hastie,Matthew Parker,David G Partridge,Cariad Evans,Timothy M. Freeman,Thushan I de Silva,Adrienne Angyal,Rebecca Brown,Laura Carrilero,Luke R. Green,Luke R. Green,Luke R. Green,Danielle C. Groves,Katie Johnson,Alexander J Keeley,Benjamin B Lindsey,Paul J. Parsons,Mohammad Raza,Sarah Rowland-Jones,Nikki Smith,Rachel Tucker,Dennis Wang,Matthew Wyles,Charlene McDanal,Lautaro G. Perez,Haili Tang,Alex Moon-Walker,Alex Moon-Walker,Alex Moon-Walker,Sean P. J. Whelan,Celia C. LaBranche,Erica Ollmann Saphire,David C. Montefiori +42 more
TL;DR: A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic, and it is found that the G614 variant grows to higher titer as pseudotyped virions.
Journal ArticleDOI
SARS and MERS: recent insights into emerging coronaviruses
TL;DR: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronav virus into the human population in the twenty-first century, and the current state of development of measures to combat emerging coronaviruses is discussed.
Journal ArticleDOI
Emerging coronaviruses: Genome structure, replication, and pathogenesis.
Yu Chen,Qianyun Liu,Deyin Guo +2 more
TL;DR: This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats and describe diseases caused by different CoVs in humans and animals.
Journal ArticleDOI
Spike mutation D614G alters SARS-CoV-2 fitness.
Jessica A. Plante,Yang Liu,Jianying Liu,Hongjie Xia,Bryan A. Johnson,Kumari G. Lokugamage,Xianwen Zhang,Antonio E. Muruato,Jing Zou,Camila R. Fontes-Garfias,Divya Mirchandani,Dionna Scharton,John P. Bilello,Zhiqiang Ku,Zhiqiang An,Birte Kalveram,Alexander N. Freiberg,Vineet D. Menachery,Xuping Xie,Kenneth S. Plante,Scott C. Weaver,Pei Yong Shi +21 more
TL;DR: Hamsters infected with SARS-CoV-2 expressing spike D614G (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission.
Journal ArticleDOI
Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease
Maria L. Agostini,Erica L. Andres,Amy C. Sims,Rachel L. Graham,Timothy P. Sheahan,Xiaotao Lu,Everett Clinton Smith,Everett Clinton Smith,James Brett Case,Joy Y. Feng,Robert Jordan,Adrian S. Ray,Tomas Cihlar,Dustin Siegel,Richard L. Mackman,Michael O'neil Hanrahan Clarke,Ralph S. Baric,Mark R. Denison +17 more
TL;DR: It is shown that GS-5734 inhibits murine hepatitis virus (MHV) with similar 50% effective concentration values (EC50) as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS- coV) and that resistance can be overcome with increased, nontoxic concentrations of GS- 5734, further supporting the development of GS -5734 as a broad-spectrum therapeutic to protect against contemporary and emerging CoVs.
References
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TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.
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TL;DR: The novel coronavirus might have a role in causing SARS and was detected in a variety of clinical specimens from patients with SARS but not in controls.
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Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease
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