Search

The coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created an unprecedented threat to public health. The pandemic has been sweeping the globe, impacting more than 200 countries, with more outbreaks still lurking on the horizon. At the time of the writing, no approved drugs or vaccines are available to treat COVID-19 patients, prompting an urgent need to decipher mechanisms underlying the pathogenesis and develop curative treatments. To fight COVID-19, researchers around the world have provided specific tools and molecular information for SARS-CoV-2. These pieces of information can be integrated to aid computational investigations and facilitate clinical research. This paper reviews current knowledge, the current status of drug development and various resources for key steps toward effective treatment of COVID-19, including the phylogenetic characteristics, genomic conservation and interaction data. The final goal of this paper is to provide information that may be utilized in bioinformatics approaches and aid target prioritization and drug repurposing. Several SARS-CoV-2-related tools/databases were reviewed, and a web-portal named OverCOVID (http://bis.zju.edu.cn/overcovid/) is constructed to provide a detailed interpretation of SARS-CoV-2 basics and share a collection of resources that may contribute to therapeutic advances. These information could improve researchers' understanding of SARS-CoV-2 and help to accelerate the development of new antiviral treatments. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has impacted public health as well as societal and economic well-being. In the last two decades, various prediction algorithms and tools have been developed for predicting antiviral peptides (AVPs). The current COVID-19 pandemic has underscored the need to develop more efficient and accurate machine learning (ML)-based prediction algorithms for the rapid identification of therapeutic peptides against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Several peptide-based ML approaches, including anti-coronavirus peptides (ACVPs), IL-6 inducing epitopes and other epitopes targeting SARS-CoV-2, have been implemented in COVID-19 therapeutics. Owing to the growing interest in the COVID-19 field, it is crucial to systematically compare the existing ML algorithms based on their performances. Accordingly, we comprehensively evaluated the state-of-the-art IL-6 and AVP predictors against coronaviruses in terms of core algorithms, feature encoding schemes, performance evaluation metrics and software usability. A comprehensive performance assessment was then conducted to evaluate the robustness and scalability of the existing predictors using well-constructed independent validation datasets. Additionally, we discussed the advantages and disadvantages of the existing methods, providing useful insights into the development of novel computational tools for characterizing and identifying epitopes or ACVPs. The insights gained from this review are anticipated to provide critical guidance to the scientific community in the rapid design and development of accurate and efficient next-generation in silico tools against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Human coronaviruses (CoVs) can cause respiratory infection epidemics that sometimes expand into globally relevant pandemics. All human CoVs have sister strains isolated from animal hosts and seem to have an animal origin, yet the process of host jumping is largely unknown. RNA interference (RNAi) is an ancient mechanism in many eukaryotes to defend against viral infections through the hybridization of host endogenous small RNAs (miRNAs) with target sites in invading RNAs. Here, we developed a method to identify potential RNAi-sensitive sites in the viral genome and discovered that human-adapted coronavirus strains had deleted some of their sites targeted by miRNAs in human lungs when compared to their close zoonic relatives. We further confirmed using a phylogenetic analysis that the loss of RNAi-sensitive target sites could be a major driver of the host-jumping process, and adaptive mutations that lead to the loss-of-target might be as simple as point mutation. Up-to-date genomic data of severe acute respiratory syndrome coronavirus 2 and Middle-East respiratory syndromes-CoV strains demonstrate that the stress from host miRNA milieus sustained even after their epidemics in humans. Thus, this study illustrates a new mechanism about coronavirus to explain its host-jumping process and provides a novel avenue for pathogenesis research, epidemiological modeling, and development of drugs and vaccines against coronavirus, taking into consideration these findings. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals that have hypertension or cardiovascular comorbidities have an elevated risk of serious coronavirus disease 2019 (COVID-19) disease and high rates of mortality but how COVID- |$19$| and cardiovascular diseases interact are unclear. We therefore sought to identify novel mechanisms of interaction by identifying genes with altered expression in SARS-CoV- |$2$| infection that are relevant to the pathogenesis of cardiovascular disease and hypertension. Some recent research shows the SARS-CoV- |$2$| uses the angiotensin converting enzyme- |$2$| (ACE- |$2$|⁠) as a receptor to infect human susceptible cells. The ACE2 gene is expressed in many human tissues, including intestine, testis, kidneys, heart and lungs. ACE2 usually converts Angiotensin I in the renin–angiotensin-aldosterone system to Angiotensin II, which affects blood pressure levels. ACE inhibitors prescribed for cardiovascular disease and hypertension may increase the levels of ACE- |$2$|⁠ , although there are claims that such medications actually reduce lung injury caused by COVID- |$19$|⁠. We employed bioinformatics and systematic approaches to identify such genetic links, using messenger RNA data peripheral blood cells from COVID- |$19$| patients and compared them with blood samples from patients with either chronic heart failure disease or hypertensive diseases. We have also considered the immune response genes with elevated expression in COVID- |$19$| to those active in cardiovascular diseases and hypertension. Differentially expressed genes (DEGs) common to COVID- |$19$| and chronic heart failure, and common to COVID- |$19$| and hypertension, were identified; the involvement of these common genes in the signalling pathways and ontologies studied. COVID- |$19$| does not share a large number of differentially expressed genes with the conditions under consideration. However, those that were identified included genes playing roles in T cell functions, toll-like receptor pathways, cytokines, chemokines, cell stress, type 2 diabetes and gastric cancer. We also identified protein–protein interactions, gene regulatory networks and suggested drug and chemical compound interactions using the differentially expressed genes. The result of this study may help in identifying significant targets of treatment that can combat the ongoing pandemic due to SARS-CoV- |$2$| infection. [ABSTRACT FROM AUTHOR]

Accessory proteins play important roles in the interaction between coronaviruses and their hosts. Accordingly, a comprehensive study of the compositional diversity and evolutionary patterns of accessory proteins is critical to understanding the host adaptation and epidemic variation of coronaviruses. Here, we developed a standardized genome annotation tool for coronavirus (CoroAnnoter) by combining open reading frame prediction, transcription regulatory sequence recognition and homologous alignment. Using CoroAnnoter, we annotated 39 representative coronavirus strains to form a compositional profile for all of the accessary proteins. Large variations were observed in the number of accessory proteins of 1–10 for different coronaviruses, with SARS-CoV-2 and SARS-CoV having the most (9 and 10, respectively). The variation between SARS-CoV and SARS-CoV-2 accessory proteins could be traced back to related coronaviruses in other hosts. The genomic distribution of accessory proteins had significant intra-genus conservation and inter-genus diversity and could be grouped into 1, 4, 2 and 1 types for alpha-, beta-, gamma-, and delta-coronaviruses, respectively. Evolutionary analysis suggested that accessory proteins are more conservative locating before the N-terminal of proteins E and M (E-M), while they are more diverse after these proteins. Furthermore, comparison of virus-host interaction networks of SARS-CoV-2 and SARS-CoV accessory proteins showed that they share multiple antiviral signaling pathways, those involved in the apoptotic process, viral life cycle and response to oxidative stress. In summary, our study provides a tool for coronavirus genome annotation and builds a comprehensive profile for coronavirus accessory proteins covering their composition, classification, evolutionary pattern and host interaction. [ABSTRACT FROM AUTHOR]