ABSTRACT
Host-viral interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics. N6-methyladenosine modification (m6A), one of the most abundant cellular RNA modifications, regulates key processes in RNA metabolism during a stress response. Gene expression profiles observed post-infection with different SARS-CoV-2 variants show changes in the expression of genes related to RNA catabolism, including m6A readers and erasers. We found that infection with SARS-CoV-2 variants caused a loss of m6A in cellular RNAs, whereas m6A was detected abundantly in viral RNA. METTL3, the m6A methyltransferase, showed an unusual cytoplasmic localization post-infection. The B.1.351 variant had a less pronounced effect on METTL3 localization and loss of m6A than the B.1 and B.1.1.7 variants. We also observed a loss of m6A upon SARS-CoV-2 infection in air/liquid interface cultures of human airway epithelia, confirming that m6A loss is characteristic of SARS-CoV-2 infected cells. Further, transcripts with m6A modification were preferentially down-regulated post-infection. Inhibition of the export protein XPO1 resulted in the restoration of METTL3 localization, recovery of m6A on cellular RNA, and increased mRNA expression. Stress granule formation, which was compromised by SARS-CoV-2 infection, was restored by XPO1 inhibition and accompanied by a reduced viral infection in vitro. Together, our study elucidates how SARS-CoV-2 inhibits the stress response and perturbs cellular gene expression in an m6A-dependent manner.
Subject(s)
Severe Acute Respiratory Syndrome , Virus Diseases , COVID-19ABSTRACT
It’s been more than 2 years since the first outbreak of COVID-19, and still the pandemic is devastating the world and is standing as significant threat to the worldwide medical settings. The reports of new variants, absence of globally approved therapeutics are the major reasons responsible for the continuously increasing number of cases and mortalities. The main protease (Mpro) of SARS-CoV-2 is a well reported and a key therapeutic target for designing drugs to treat COVID-19. The medicinal properties of mushrooms and its derived natural compounds are well established. Here in this study, we have performed the virtual screening of mushroom-derived compounds against the SARS-CoV-2 Mpro. Cordycepin was found to be the most active compound against Mpro. The compound was further isolated from C. militaris and in vitro assay was performed to confirm its antivirals potential against SARS-CoV-2. Our findings show cordycepin to be a promising candidate against COVID-19.
Subject(s)
COVID-19ABSTRACT
The ongoing coronavirus disease 2019 (COVID-19) pandemic has become a serious global threat. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for this pandemic has imposed a severe burden on the medical settings. The spike (S) protein of SARS-CoV-2 is an important structural protein playing a key role in the viral entry. This protein is responsible for the receptor recognition and cell membrane fusion process. The recent reports of the appearance and spread of new SARS-CoV-2 strain has raised alarms. It was reported that this new variant containing the prominent active site mutation in the RBD (N501Y) was rapidly spreading within the population. The reported N501Y mutation within the spike's essential part, known as the ‘receptor-binding domain’ has raised several questions. Here in this study we have tried to explore the effect of N501Y mutation within the spike protein using several in silico approaches
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
The ongoing coronavirus disease 2019 (COVID-19) pandemic has become a serious global threat. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for this pandemic has imposed a severe burden on the medical settings. The spike (S) protein of SARS-CoV-2 is an important structural protein playing a key role in the viral entry. This protein is responsible for the receptor recognition and cell membrane fusion process. The recent reports of the appearance and spread of new SARS-CoV-2 strain has raised alarms. It was reported that this new variant containing the prominent active site mutation in the RBD (N501Y) was rapidly spreading within the population. The reported N501Y mutation within the spike's essential part, known as the receptor-binding domain has raised several questions. Here in this study we have tried to explore the effect of N501Y mutation within the spike protein using several in silico approaches
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
COVID-19, caused by SARS-CoV-2, was first reported in China in 2019 and has transmitted rapidly around the world, currently responsible for 83 million reported cases and over 1.8 million deaths. The mode of transmission is believed principally to be airborne exposure to respiratory droplets from symptomatic and asymptomatic patients but there is also a risk of the droplets contaminating fomites such as touch surfaces including door handles, stair rails etc, leading to hand pick up and transfer to eyes, nose and mouth. We have previously shown that human coronavirus 229E survives for more than 5 days on inanimate surfaces and another laboratory reproduced this for SARS-CoV-2 this year. However, we showed rapid inactivation of Hu-CoV-229E within 10 minutes on different copper surfaces while the other laboratory indicated this took 4 hours for SARS-CoV-2. So why the difference? We have repeated our work with SARS-CoV-2 and can confirm that this coronavirus can be inactivated on copper surfaces in as little as 1 minute. We discuss why the 4 hour result may be technically flawed.