scholarly journals Palmitoylation of SARS-CoV-2 S protein is essential for viral infectivity

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhuanchang Wu ◽  
Zhaoying Zhang ◽  
Xin Wang ◽  
Jing Zhang ◽  
Caiyue Ren ◽  
...  
Keyword(s):  
Author(s):  
Haijun Tang ◽  
Long Gao ◽  
Zhao Wu ◽  
Fang Meng ◽  
Xin Zhao ◽  
...  

SARS-coronavirus 2 (SARS-CoV-2), pathogen of coronavirus disease 2019 (COVID-19), is constantly evolving to adapt to the host and evade antiviral immunity. The newly emerging variants N501Y.V1 (B.1.1.7) and N501Y.V2 (B.1.351), first reported in the United Kingdom and South Africa respectively, raised concerns due to the unusually rapid global spread. The mutations in spike (S) protein may contribute to the rapid spread of these variants. Here, with a vesicular stomatitis virus (VSV)-based pseudotype system, we demonstrated that the pseudovirus bearing N501Y.V2 S protein has higher infection efficiency than pseudovirus with wildtype (WT) and D614G S protein. Moreover, pseudovirus with N501Y.V1 or N501Y.V2 S protein has better thermal stability than WT and D614G, suggesting these mutations of variants may increase the stability of SARS-CoV-2 S protein and virion. However, the pseudovirus bearing N501Y.V1 or N501Y.V2 S protein has similar sensitivity to inhibitors of protease and endocytosis with WT and D614G. These findings could be of value in preventing the spread of virus and developing drugs for emerging SARS-CoV-2 variants.


Author(s):  
Seiya Ozono ◽  
Yanzhao Zhang ◽  
Hirotaka Ode ◽  
Toong Seng Tan ◽  
Kazuo Imai ◽  
...  

AbstractThe causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is steadily mutating during continuous transmission among humans. Such mutations can occur in the spike (S) protein that binds to the angiotensin-converting enzyme-2 (ACE2) receptor and is cleaved by transmembrane protease serine 2 (TMPRSS2). However, whether S mutations affect SARS-CoV-2 infectivity remains unknown. Here, we show that naturally occurring S mutations can reduce or enhance cell entry via ACE2 and TMPRSS2. A SARS-CoV-2 S-pseudotyped lentivirus exhibits substantially lower entry than SARS-CoV S. Among S variants, the D614G mutant shows the highest cell entry, as supported by structural observations. Nevertheless, the D614G mutant remains susceptible to neutralization by antisera against prototypic viruses. Taken together, these data indicate that the D614G mutation enhances viral infectivity while maintaining neutralization susceptibility.


2021 ◽  
Vol 22 (16) ◽  
pp. 9087
Author(s):  
Hsin-I Wang ◽  
Zih-Shiuan Chuang ◽  
Yu-Ting Kao ◽  
Yi-Ling Lin ◽  
Jian-Jong Liang ◽  
...  

The SARS-CoV-2 pseudovirus is a commonly used strategy that mimics certain biological functions of the authentic virus by relying on biological legitimacy at the molecular level. Despite the fact that spike (S), envelope (E), and membrane (M) proteins together wrap up the SARS-CoV-2 virion, most of the reported pseudotype viruses consist of only the S protein. Here, we report that the presence of E and M increased the virion infectivity by promoting the S protein priming. The S, E, and M (SEM)-coated pseudovirion is spherical, containing crown-like spikes on the surface. Both S and SEM pseudoviruses packaged the same amounts of viral RNA, but the SEM virus bound more efficiently to cells stably expressing the viral receptor human angiotensin-converting enzyme II (hACE2) and became more infectious. Using this SEM pseudovirus, we examined the infectivity and antigenic properties of the natural SARS-CoV-2 variants. We showed that some variants have higher infectivity than the original virus and that some render the neutralizing plasma with lower potency. These studies thus revealed possible mechanisms of the dissemination advantage of these variants. Hence, the SEM pseudovirion provides a useful tool to evaluate the viral infectivity and capability of convalescent sera in neutralizing specific SARS-CoV-2 S dominant variants.


Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
S Chillappagari ◽  
V Garapati ◽  
P Mahavadi ◽  
O Stehling ◽  
R Lill ◽  
...  
Keyword(s):  

Author(s):  
Mario Coccia

BACKGROUND Coronavirus disease 2019 (COVID-19) is viral infection that generates a severe acute respiratory syndrome with serious pneumonia that may result in progressive respiratory failure and death. OBJECTIVE This study has two goals. The first is to explain the main factors determining the diffusion of COVID-19 that is generating a high level of deaths. The second is to suggest a strategy to cope with future epidemic threats with of accelerated viral infectivity in society. METHODS Correlation and regression analyses on on data of N=55 Italian province capitals, and data of infected individuals at as of April 2020. RESULTS The main results are: o The accelerate and vast diffusion of COVID-19 in North Italy has a high association with air pollution. o Hinterland cities have average days of exceeding the limits set for PM10 (particulate matter 10 micrometers or less in diameter) equal to 80 days, and an average number of infected more than 2,000 individuals as of April 1st, 2020, coastal cities have days of exceeding the limits set for PM10 equal to 60 days and have about 700 infected in average. o Cities that average number of 125 days exceeding the limits set for PM10, last year, they have an average number of infected individual higher than 3,200 units, whereas cities having less than 100 days (average number of 48 days) exceeding the limits set for PM10, they have an average number of about 900 infected individuals. o The results reveal that accelerated transmission dynamics of COVID-19 in specific environments is due to two mechanisms given by: air pollution-to-human transmission and human-to-human transmission; in particular, the mechanisms of air pollution-to-human transmission play a critical role rather than human-to-human transmission. o The finding here suggests that to minimize future epidemic similar to COVID-19, the max number of days per year in which cities can exceed the limits set for PM10 or for ozone, considering their meteorological condition, is less than 50 days. After this critical threshold, the analytical output here suggests that environmental inconsistencies because of the combination between air pollution and meteorological conditions (with high moisture%, low wind speed and fog) trigger a take-off of viral infectivity (accelerated epidemic diffusion) with damages for health of population, economy and society. CONCLUSIONS Considering the complex interaction between air pollution, meteorological conditions and biological characteristics of viral infectivity, lessons learned for COVID-19 have to be applied for a proactive socioeconomic strategy to cope with future epidemics, especially an environmental policy based on reduction of air pollution mainly in hinterland zones of countries, having low wind speed, high percentage of moisture and fog that create an environment that can damage immune system of people and foster a fast transmission of viral infectivity similar to the COVID-19. CLINICALTRIAL not applicable


2003 ◽  
Vol 77 (13) ◽  
pp. 7539-7544 ◽  
Author(s):  
Ayato Takada ◽  
Heinz Feldmann ◽  
Thomas G. Ksiazek ◽  
Yoshihiro Kawaoka

ABSTRACT Most strains of Ebola virus cause a rapidly fatal hemorrhagic disease in humans, yet there are still no biologic explanations that adequately account for the extreme virulence of these emerging pathogens. Here we show that Ebola Zaire virus infection in humans induces antibodies that enhance viral infectivity. Plasma or serum from convalescing patients enhanced the infection of primate kidney cells by the Zaire virus, and this enhancement was mediated by antibodies to the viral glycoprotein and by complement component C1q. Our results suggest a novel mechanism of antibody-dependent enhancement of Ebola virus infection, one that would account for the dire outcome of Ebola outbreaks in human populations.


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