Hydrodynamics of spike proteins dictate a transport-affinity competition for SARS-CoV-2 and other enveloped viruses

Many viruses, such as SARS-CoV-2 or Influenza, possess spike-decorated envelopes. Depending on the virus type, a large variability is present in spikes number, morphology and reactivity, which remains generally unexplained. Since viruses' transmissibility depend on features beyond their genetic sequence, new tools are required to discern the effects of spikes functionality, interaction, and morphology. Here, we postulate the relevance of hydrodynamic interactions in the viral infectivity of enveloped viruses and propose micro-rheological characterization as a platform for viruses differentiation. To understand how the spikes affect virion mobility and infectivity, we investigate the diffusivity of spike-decorate structures using mesoscopic-hydrodynamic simulations. Furthermore, we explored the interplay between affinity and passive viral transport. Our results revealed that the diffusional mechanism of SARS-CoV-2 is strongly influenced by the size and distribution of its spikes. We propose and validate a universal mechanism to explain the link between optimal virion structure and maximal infectivity for many virus families.

Advances in the Development of Antiviral Compounds for Rotavirus Infections

ABSTRACT Group A rotaviruses (RVAs) are the major cause of severe acute gastroenteritis (AGE) in children under 5 years of age, annually resulting in nearly 130,000 deaths worldwide. Social conditions in developing countries that contribute to decreased oral rehydration and vaccine efficacy and the lack of approved antiviral drugs position RVA as a global health concern. In this minireview, we present an update in the field of antiviral compounds, mainly in relation to the latest findings in RVA virion structure and the viral replication cycle. In turn, we attempt to provide a perspective on the possible treatments for RVA-associated AGE, with special focus on novel approaches, such as those representing broad-spectrum therapeutic options. In this context, the modulation of host factors, lipid droplets, and the viral polymerase, which is highly conserved among AGE-causing viruses, are analyzed as possible drug targets.

The Novel Coronavirus (nCoV) – A Worldwide Threat

This review aims to asses the data from recently published literature related to the novel Coronavirus (nCoV), which had been isolated in the automn of 2019. Similarly to the classical Coronavirus (cCoV) isolated nearly 18 years ago, the nCoV has also emerged in China, though in a different region of the same country. The majority of papers published in the current year 2020, clearly demonstrates the actual nature of the given topics. Despite of the unusual criteria used for information selection, all the collected data have turned up useful as the virion structure and its properties concerns. Neither were omitted the clinical signs of virus related disease(s) nor understanding the spread of any other pathological state(s) occurring in infected patients. Last but not least, the presented epidemiological data contribute to understanding the spread of nCoV in human community(ies).

Fundamental Difficulties Prevent the Reconstruction of the Deep Phylogeny of Viruses

The extension of virology beyond its traditional medical, veterinary, or agricultural applications, now called environmental virology, has shown that viruses are both the most numerous and diverse biological entities on Earth. In particular, virus isolations from unicellular eukaryotic hosts (heterotrophic and photosynthetic protozoans) revealed numerous viral types previously unexpected in terms of virion structure, gene content, or mode of replication. Complemented by large-scale metagenomic analyses, these discoveries have rekindled interest in the enigma of the origin of viruses, for which a description encompassing all their diversity remains not available. Several laboratories have repeatedly tackled the deep reconstruction of the evolutionary history of viruses, using various methods of molecular phylogeny applied to the few shared “core” genes detected in certain virus groups (e.g., the Nucleocytoviricota). Beyond the practical difficulties of establishing reliable homology relationships from extremely divergent sequences, I present here conceptual arguments highlighting several fundamental limitations plaguing the reconstruction of the deep evolutionary history of viruses, and even more the identification of their unique or multiple origin(s). These arguments also underline the risk of establishing premature high level viral taxonomic classifications. Those limitations are direct consequences of the random mechanisms governing the reductive/retrogressive evolution of all obligate intracellular parasites.

Virion Structure and Mechanism of Propagation of Coronaviruses including SARS-CoV 2 (COVID -19 ) and some Meaningful Points for Drug or Vaccine Development

SARS-CoV-2 or COVID-19, a new seventh human corona virus, has out-broken in Wuhan, China since 31st December 2019, and quickly escalated to take the form of pandemic which killed many human beings throughout almost all countries across continents. The rapidity of its transmission from human to human is far greater than all previous human corona viruses which came into existence like SARS-CoV, MERS-CoV, etc. The nucleotide sequence of SARS-CoV-2 (isolates Wuhan-Hu-1) is 29,875 bp in ss-RNA. Symptoms of SARS-CoV-2 infected pneumonia include from asymptomatic to high fever and/or respiratory illnesses. Coronavirus virion (spherical/round /elliptical in shape) consists of three parts- outer membrane or envelope, nucleocapsid and genome (RNA). SARS-CoV-2 was shown to use receptor, angiotensin converting enzyme 2 (ACE2) for attachment to the cells through its surface spike (S) protein (S1), and the virion enters into the host cell through two routes- direct membrane fusion and endocytotic pathway. The RNA of SARS-CoV acts directly as mRNA and here minus(-) 1 programmed ribosomal frameshift (-1PRF) is being operated by slippery sequence and pseudoknot, so it translates 16 nonstructural proteins including RNA dependent RNA replicase. Then genomic RNA replicated continuously on – strand RNA template and subgenomic RNA transcribed discontinuously on –RNA template to sgmRNA. Subgenomic RNAs/sgmRNAs synthesize all structural proteins. This article takes into consideration the details of established theories of viral structure, viral attachment, mode of entry into human cells, different models of replication and transcription of virus genome proposed by eminent scientists over the years, and makes an in depth examination highlighting meaningful points or important target cites of viral propagation or synthesis, which are conserved, for prompt development of potent drugs or vaccine to counter COVID-19 for which human race is anxiously and eagerly waiting.

Dynamic competition for hexon binding between core protein VII and lytic protein VI promotes adenovirus maturation and entry

Adenovirus minor coat protein VI contains a membrane-disrupting peptide that is inactive when VI is bound to hexon trimers. Protein VI must be released during entry to ensure endosome escape. Hexon:VI stoichiometry has been uncertain, and only fragments of VI have been identified in the virion structure. Recent findings suggest an unexpected relationship between VI and the major core protein, VII. According to the high-resolution structure of the mature virion, VI and VII may compete for the same binding site in hexon; and noninfectious human adenovirus type 5 particles assembled in the absence of VII (Ad5-VII-) are deficient in proteolytic maturation of protein VI and endosome escape. Here we show that Ad5-VII- particles are trapped in the endosome because they fail to increase VI exposure during entry. This failure was not due to increased particle stability, because capsid disruption happened at lower thermal or mechanical stress in Ad5-VII- compared to wild-type (Ad5-wt) particles. Cryoelectron microscopy difference maps indicated that VII can occupy the same binding pocket as VI in all hexon monomers, strongly arguing for binding competition. In the Ad5-VII- map, density corresponding to the immature amino-terminal region of VI indicates that in the absence of VII the lytic peptide is trapped inside the hexon cavity, and clarifies the hexon:VI stoichiometry conundrum. We propose a model where dynamic competition between proteins VI and VII for hexon binding facilitates the complete maturation of VI, and is responsible for releasing the lytic protein from the hexon cavity during entry and stepwise uncoating.

Analysis of COVID-19 M Protein for Possible Clues Regarding Virion Stability, Longevity and Spreading

The Severe Acute Respiratory Syndrome Coronavirus 2 or COVID-19 has been the cause of a global pandemic in 2020. With the numbers infected rising well above a 100,000 and confirmed deaths above 4000, it has become the paramount health concern for the global community at present. The COVID-19 genome has since been sequenced and its predicted proteome identified. In this study, we looked at the expected COVID-19 proteins and compare them to its close relative, the Severe Acute Respiratory Syndrome-Related Coronavirus. In particular we focussed on the M protein which is known to play a significant role in the virion structure of Coronaviruses. The rationale here was that since the major risk factor associated with COVID-19 was its ease of spread, we wished to focus on the viral structure and architecture to look for clues that may indicate structural stability, thus prolonging the time span for which it can survive free of a host. As a result of the study, we found some rather interesting differences between the M protein for COVID-19 and the SARS-CoV virus M protein. This included amino acid changes from non-polar to polar residues in regions important for anchoring the protein in the envelope membrane.

Interpretation of SARS-CoV-2 behaviour on different substrates and denaturation of virions using ethanol: an atomic force microscopy study

We studied the density and aggregation behavior of virions on TCPS and glass substrates, surface functionality, coffee ring effect on both surfaces and the effect of ethanol-based disinfectant on the virion structure using atomic force microscopy.

Structure of the Macrobrachium rosenbergii Nodavirus: A new genus within the Nodaviridae?

Macrobrachium rosenbergii nodavirus (MrNV) is a pathogen of freshwater prawns that poses a threat to food-security and causes significant economic losses in the aquaculture industries of many developing nations. A detailed understanding of the MrNV virion structure will inform the development of strategies to control outbreaks. The MrNV capsid has also been engineered to display heterologous antigens, thus knowledge of its atomic resolution structure will benefit efforts to develop tools based on this platform. Here we present an atomic-resolution model of the MrNV capsid protein, calculated by cryogenic electron microscopy (cryoEM) of MrNV virus-like particles (VLPs) produced in insect cells, and three-dimensional image reconstruction at 3.3 Å resolution. CryoEM of MrNV virions purified from infected freshwater prawn post-larvae yielded a 6.6 Å resolution structure confirming the biological relevance of the VLP structure.Our data revealed that unlike other known nodaviruses structures, which have been shown to assemble capsids having trimeric spikes, MrNV assembles a T=3 capsid with dimeric spikes. We also found a number of surprising similarities between the MrNV capsid structure and that of the Tombusviridae. 1. An extensive network of N-terminal arms lines the capsid interior forming long-range interactions to lace together asymmetric units. 2. The capsid shell is stabilised by three pairs of Ca2+ ions in each asymmetric unit. 3. The protruding spike domain exhibits a very similar fold to that seen in the spikes of the tombusviruses. These structural similarities raise questions concerning the correct taxonomic classification of MrNV.