virus structure
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2022 ◽  
Author(s):  
Edward E Large ◽  
Mark A Silveria ◽  
Tommi A White ◽  
Michael S Chapman

Adeno-associated virus (AAV) is a small ssDNA satellite virus of high interest (in recombinant form) as a safe and effective gene therapy vector. AAV's human cell entry receptor (AAVR) contains Polycystic Kidney Disease (PKD) domains bound by AAV. Seeking understanding of the spectrum of interactions, goat AAVGo.1 is investigated, because its host is the species most distant from human with reciprocal cross-species cell susceptibility. The structure of AAVGo.1, solved by cryo-EM to 2.9 Å resolution, is most similar to AAV5. Through ELISA studies, it is shown that AAVGo.1 binds to human AAVR (huAAVR) more strongly than do AAV2 or AAV5, and that it joins AAV5 in a class that binds exclusively to PKD domain 1 (PKD1), in contrast to other AAVs that interact primarily with PKD2. The AAVGo.1 cryo-EM structure of a complex with a PKD12 fragment of huAAVR at 2.4 Å resolution shows PKD1 bound with minimal change in virus structure, except for disordering of a neighboring surface loop. Only 4 of the 42 capsid protein sequence differences between AAVGo.1 and AAV5 occur at the PKD1 binding interface. These result in only minor conformational changes in AAVR, including a near rigid domain rotation with maximal displacement of the receptor by ~1 Å. A picture emerges of two classes of AAV with completely different modes of binding to the same AAVR receptor, but within each class atomic interactions are mostly conserved. IMPORTANCE Adeno-Associated Virus (AAV) is a small ssDNA satellite parvovirus. As a recombinant vector with a protein shell encapsidating a transgene, recombinant AAV (rAAV) is a leading delivery vehicle for gene therapy with two FDA-approved treatments and 150 clinical trials for 30 diseases. The human entry receptor huAAVR has five PKD domains. To date, all serotypes, except AAV5, have interacted primarily with the second PKD domain, PKD2. Goat is the AAV host most distant from human with cross-species cell infectivity. AAVGo.1 is similar in structure to AAV5, the two forming a class with a distinct mode of receptor-binding. Within the two classes, binding interactions are mostly conserved, giving an indication of the latitude available in modulating delivery vectors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicole Balasco ◽  
Gianluca Damaggio ◽  
Luciana Esposito ◽  
Flavia Villani ◽  
Rita Berisio ◽  
...  

AbstractThe ability of SARS-CoV-2 to rapidly mutate represents a remarkable complicancy. Quantitative evaluations of the effects that these mutations have on the virus structure/function is of great relevance and the availability of a large number of SARS-CoV-2 sequences since the early phases of the pandemic represents a unique opportunity to follow the adaptation of the virus to humans. Here, we evaluated the SARS-CoV-2 amino acid mutations and their progression by analyzing publicly available viral genomes at three stages of the pandemic (2020 March 15th and October 7th, 2021 February 7th). Mutations were classified in conservative and non-conservative based on the probability to be accepted during the evolution according to the Point Accepted Mutation substitution matrices and on the similarity of the encoding codons. We found that the most frequent substitutions are T > I, L > F, and A > V and we observe accumulation of hydrophobic residues. These findings are consistent among the three stages analyzed. We also found that non-conservative mutations are less frequent than conservative ones. This finding may be ascribed to a progressive adaptation of the virus to the host. In conclusion, the present study provides indications of the early evolution of the virus and tools for the global and genome-specific evaluation of the possible impact of mutations on the structure/function of SARS-CoV-2 variants.


2021 ◽  
Vol 51 ◽  
pp. 16-24
Author(s):  
Zlatka Plavec ◽  
Ina Pöhner ◽  
Antti Poso ◽  
Sarah J Butcher
Keyword(s):  

2021 ◽  
Vol 11 (4) ◽  
pp. 4201-4212

Novel coronavirus (COVID-19) recently emerged as a new pandemic disease that affects millions of people worldwide. This disease considers as a potential threat to human society. Researchers are continuously working to identify virus structure, the pathophysiology of the disease, and possible treatment of the disease. Currently, to fight against the coronavirus, two major strategies have been adopted throughout the world; one is to target virus-cell machinery, and the second is to improve patient immunity. In this review, we have described detailed information about the structure and life cycle of the novel coronavirus, current therapy, and future strategies to fight against this pandemic disease. Computational methods are useful for understanding virus structure, disease pathology, and discovering novel anti-COVID agents. These methods can provide fast and efficient solutions to fight against this disease. We also highlighted the potential role of robotic technology and its importance in various clinical aspects. These robotic technologies may also play an important role in fighting COVID-19.


2021 ◽  
Vol 21 ◽  
Author(s):  
Leila Mousavizadeh ◽  
Ramin Soltani ◽  
Kosar Abedini ◽  
Sorayya Ghasemi

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has high mortality due to the widespread infection and the strong immune system reaction. Interleukins (ILs) are among the main immune factors contributing to the deterioration of the immune response and the formation of cytokine storms in coronavirus disease 2019 (COVID-19) infections. Introduction: This review article investigated the relationship between virus structure, risk factors, and patient plasma interleukin levels in infections caused by the coronavirus family. Method: The keywords "interleukin," "coronavirus structure," "plasma," and "risk factors" were the main words searched to find a relationship among different interleukins, coronavirus structures, and risk factors in ISI, PUBMED, SCOPUS, and Google Scholar databases. Results: Patients with high-risk conditions with independent panels of immune system markers are more susceptible to death caused by SARS-CoV2. IL-4, IL-10, and IL-15 are probably secreted at different levels in patients with coronavirus infections despite the similarity of inflammatory markers during coronavirus infections. SARS-CoV2 and SARS-CoV increase the secretion of IL-4 in the Middle East respiratory syndrome coronavirus (MERS-CoV) infection, while it remains unchanged in MERS-CoV infection. MERS-CoV infection demonstrates increased IL-10 levels. However, IL-10 levels increase during SARS-CoV infection, and different levels are recorded in SARS-CoV2. MERS-CoV increases IL-15 secretion while its levels remain unchanged in SARS-CoV2. Conclusion: In conclusion, the different structures of SARS-CoV2, such as length of spike or nonstructural proteins (NSPs), and susceptibility of patients based on their risk factors may lead to differences in immune marker secretion and pathogenicity. Therefore, identifying and controlling interleukin levels can play a significant role in controlling the symptoms and the development of individual-specific treatments.


Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1201
Author(s):  
Alexander Hargreaves ◽  
Caolann Brady ◽  
Jack Mellors ◽  
Tom Tipton ◽  
Miles W. Carroll ◽  
...  

Filoviruses, especially Ebola virus, cause sporadic outbreaks of viral haemorrhagic fever with very high case fatality rates in Africa. The 2013–2016 Ebola epidemic in West Africa provided large survivor cohorts spurring a large number of human studies which showed that specific neutralising antibodies played a key role in protection following a natural Ebola virus infection, as part of the overall humoral response and in conjunction with the cellular adaptive response. This review will discuss the studies in survivors and animal models which described protective neutralising antibody response. Their mechanisms of action will be detailed. Furthermore, the importance of neutralising antibodies in antibody-based therapeutics and in vaccine-induced responses will be explained, as well as the strategies to avoid immune escape from neutralising antibodies. Understanding the neutralising antibody response in the context of filoviruses is crucial to furthering our understanding of virus structure and function, in addition to improving current vaccines & antibody-based therapeutics.


2021 ◽  
Vol 18 (2) ◽  
pp. 385-393
Author(s):  
Viswanath Vittaladevaram ◽  
Kranthi Kuruti ◽  
Sudheer Venkatesh Urity

The evolution of COVID-19 across the globe is rapid due to increased mobility which spreads and evolves continuously among human population. Based on phylogenetic analysis the virus is termed as SARS-COV-2 (Severe acute respiratory syndrome coronavirus 2) which spreads rapidly among human beings. The article focuses on aspects of virus structure, organization of genome, epidemiological characteristics, mode of transmission and global impact of Coronavirus. In addition to this, diagnosis and pharmacological approach, treatment, prevention procedures and vaccines that are currently in use were highlighted.


2021 ◽  
Vol 7 (2) ◽  
pp. 124-133
Author(s):  
Jaydip Jikadara ◽  
◽  
Samresh Pal Roy ◽  

The present review focuses on the overview of the immune system regarding its protection of the human body against COVID-19 virus; illustrates the immunity boosting activity of herbal plants against SARS-CoV-2 infection. This work also provides information regarding virus structure information, immunopathogensis of virus with human body and role of Ayurveda in coronavirus disease. A number of herbal plants based active principles have been isolated and extracted with potential immunostimulant and immunosuppressant activity that can explain their beneficial use in traditional medicine and form the further research base for the future studies. The goal of this review is to foreground the immunity boosting activity of different herbal plants and its beneficial use in COVID-19 disease. Many plants and their phytochemicals, responsible for immunomodulation mechanism in SARS-CoV-2 infection have been explained. This review shall hopefully encourage researchers to undertake further work on herbal or medicinal plants with potential immunity boosting activity in COVID-19 disease.


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