•Journal•ISSN: 2673-818X
Frontiers in virology
Frontiers Media
About: Frontiers in virology is an academic journal published by Frontiers Media. The journal publishes majorly in the area(s): Biology & Medicine. It has an ISSN identifier of 2673-818X. It is also open access. Over the lifetime, 133 publications have been published receiving 213 citations.
Topics: Biology, Medicine, Immunology, Virus, Gene
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TL;DR: This review unravels the complex network of interactions between SARS-CoV-2 and the host cell, highlighting the knowledge that has the potential to set the basis for the development of innovative antiviral strategies.
Abstract: The ability of a virus to spread between individuals, its replication capacity and the clinical course of the infection are macroscopic consequences of a multifaceted molecular interaction of viral components with the host cell. The heavy impact of COVID-19 on the world population, economics and sanitary systems calls for therapeutic and prophylactic solutions that require a deep characterization of the interactions occurring between virus and host cells. Unveiling how SARS-CoV-2 engages with host factors throughout its life cycle is therefore fundamental to understand the pathogenic mechanisms underlying the viral infection and to design antiviral therapies and prophylactic strategies. Two years into the SARS-CoV-2 pandemic, this review provides an overview of the interplay between SARS-CoV-2 and the host cell, with focus on the machinery and compartments pivotal for virus replication and the antiviral cellular response. Starting with the interaction with the cell surface, following the virus replicative cycle through the characterization of the entry pathways, the survival and replication in the cytoplasm, to the mechanisms of egress from the infected cell, this review unravels the complex network of interactions between SARS-CoV-2 and the host cell, highlighting the knowledge that has the potential to set the basis for the development of innovative antiviral strategies.
26 citations
TL;DR: The electrostatic potential surface of the Spike protein is mapped to show that major SARS-CoV-2 variants have accumulated positive charges in solvent-exposed regions of the spike protein, especially its ACE2-binding interface, which suggests electrostatic interactions are a major contributing factor for increased Omicron transmissibility relative to other variants.
Abstract: High transmissibility is a hallmark of the Omicron variant of SARS-CoV-2. Understanding the molecular determinants of Omicron’s transmissibility will impact development of intervention strategies. Here we map the electrostatic potential surface of the Spike protein to show that major SARS-CoV-2 variants have accumulated positive charges in solvent-exposed regions of the Spike protein, especially its ACE2-binding interface. Significantly, the Omicron Spike-ACE2 complex has complementary electrostatic surfaces. In contrast, interfaces between Omicron and neutralizing antibodies tend to have similar positively charged surfaces. Structural modeling demonstrates that the electrostatic property of Omicron’s Spike receptor binding domain (S RBD) plays a role in enhancing ACE2 recognition and destabilizing Spike-antibody complexes. Collectively, our structural analysis implies that Omicron S RBD interaction interfaces have been optimized to simultaneously promote access to human ACE2 receptors and evade antibodies. These findings suggest that electrostatic interactions are a major contributing factor for increased Omicron transmissibility relative to other variants.
24 citations
TL;DR: In this paper , the structure of the spike protein's receptor binding domain was predicted to change, which may reduce antibody interaction without completely evading existing neutralizing antibodies and therefore current vaccines.
Abstract: The genome of the SARS-CoV-2 Omicron variant (B.1.1.529) was released on November 22, 2021, which has caused a flurry of media attention due the large number of mutations it contains. These raw data have spurred questions around vaccine efficacy. Given that neither the structural information nor the experimentally-derived antibody interaction of this variant are available, we have turned to predictive computational methods to model the mutated structure of the spike protein's receptor binding domain and posit potential changes to vaccine efficacy. In this study, we predict some structural changes in the receptor-binding domain that may reduce antibody interaction without completely evading existing neutralizing antibodies (and therefore current vaccines).
16 citations
TL;DR: The symptoms reported most frequently during the early phases of the pandemic by SARS-CoV-2 infected individuals were tiredness, headache, impairment of smell or taste and dry cough; with the spread of the alpha and delta variants, the frequency of nose symptoms such as blocked or runny nose and sneezing increased to being reported by almost 60% of infected individuals.
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic and public health crisis since the beginning of 2020. First recognized for the induction of severe disease, the virus also causes asymptomatic infections or infections with mild symptoms that can resemble common colds. To provide better understanding of these mild SARS-CoV-2 infections and to monitor the development of symptoms over time, we performed a detailed analysis of self-reported symptoms of SARS-CoV-2 positive and SARS-CoV-2 negative individuals. In an online-based survey, a total of 2117 individuals provided information on symptoms associated with an acute respiratory infection, 1925 of the participants had tested positive for SARS-CoV-2 infection, and 192 had tested negative. The symptoms reported most frequently during the early phases of the pandemic by SARS-CoV-2 infected individuals were tiredness, headache, impairment of smell or taste and dry cough. With the spread of the alpha and delta variants, the frequency of nose symptoms such as blocked or runny nose and sneezing increased to being reported by almost 60% of infected individuals. Interestingly, the spread of the omicron variant brought a sharp decrease in the incidence of impaired sense of smell or taste, which was reported by only 24% in this phase of the pandemic. The constellation of symptoms should be monitored closely in the months ahead, since future SARS-CoV-2 variants are likely to bring about more changes.
13 citations
TL;DR: Emerging data indicates decreasing circulating antibody levels as well as decreases in other immune correlates in vaccinated individuals, which must be interpreted with caution taking into consideration vaccine waning and the degree of vaccine variant-mismatch resulting in adaptive immune evasion by novel emerging SARS-CoV-2 variants.
Abstract: The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, is responsible for over 400 million cases and over 5. 5 million deaths worldwide. In response to widespread SARS-CoV-2 infection, immunization of the global population has approached 60% one dose and 54% full dose vaccination status. Emerging data indicates decreasing circulating antibody levels as well as decreases in other immune correlates in vaccinated individuals. Complicating the determination of vaccine effectiveness is the concomitant emergence of novel SARS-CoV-2 variants with substantial antigenic differences from the ancestral D614G strain. The Omicron variant (B.1.1.529) spike protein has over 30 mutations compared with the D614G spike protein, which was used to design most SARS-CoV-2 vaccines in use today. Therefore, breakthrough cases of SARS-CoV-2 infections or severe disease in fully vaccinated individuals must be interpreted with caution taking into consideration vaccine waning and the degree of vaccine variant-mismatch resulting in adaptive immune evasion by novel emerging SARS-CoV-2 variants.
12 citations