Genetics of Severe Acute Respiratory Syndrome Coronavirus-2 and Diagnosis of Coronavirus Disease-2019: An Overview

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a positive sense, single-stranded RNA virus, responsible for the ‘coronavirus disease-2019’ (COVID-19) pandemic. SARS-CoV-2 belongs to the sarbecovirus (lineage-B) sub-genus within the betacoronavirus genus of the coronaviridae family. SARS-CoV-2 shares similarities with SARS-CoV, which was responsible for the 2003 SARS epidemic. SARS-CoV-2 binds with great affinity to the Angiotensin Converting Enzyme-2 receptors on human cells, and its ~30 kilobases long RNA genome hijacks the host machinery and compromises the host immune system with the help of accessory proteins, such as non-structural proteins, resulting in a widespread infection. The spike protein is responsible for the contagious nature of SARS-CoV-2 and, together with the nucleocapsid protein, elicits the host inflammatory response. Several real-time reverse transcriptase polymerase chain reaction (rRT-PCR) tests have been developed to confirm SARS-CoV-2 infection in suspected cases of COVID-19. Furthermore, rapid tests based on SARS-CoV-2-specific antigens and antibodies have been developed to conduct epidemiological surveillance of the hotspot regions that are worst affected by the COVID-19 pandemic. Until effective measures to prevent the occurrence or spread of COVID-19 pandemic are developed, containment measures are being taken, such as isolation of confirmed COVID-19 patients, quarantine of individuals who may have come in contact with a SARS-CoV-2 infected individual, community-wide social distancing, state/nation-wide lockdown, etc. Several vaccines and drugs are being tested that could target the viral structural proteins, non-structural proteins or associated SARS-CoV-2 sub-genomic RNA regions.

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Prediction of SARS-CoV-2 hosts among Brazilian mammals and new coronavirus transmission chain using evolutionary bioinformatics

Animal Diseases ◽

10.1186/s44149-021-00020-w ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Luciano Rodrigo Lopes ◽

Giancarlo de Mattos Cardillo ◽

Natália Carvalho de Lucca Pina ◽

Antonio Carlos da Silva Junior ◽

Silvana Kertzer Kasinski ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Angiotensin Converting Enzyme ◽

Epidemiological Surveillance ◽

Central Position ◽

Converting Enzyme ◽

Intermediate Hosts ◽

Wild Mammals ◽

Angiotensin Converting Enzyme 2 ◽

Transmission Chain ◽

Maned Wolf

AbstractSevere acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 are thought to transmit to humans via wild mammals, especially bats. However, evidence for direct bat-to-human transmission is lacking. Involvement of intermediate hosts is considered a reason for SARS-CoV-2 transmission to humans and emergence of outbreak. Large biodiversity is found in tropical territories, such as Brazil. On the similar line, this study aimed to predict potential coronavirus hosts among Brazilian wild mammals based on angiotensin-converting enzyme 2 (ACE2) sequences using evolutionary bioinformatics. Cougar, maned wolf, and bush dogs were predicted as potential hosts for coronavirus. These indigenous carnivores are philogenetically closer to the known SARS-CoV/SARS-CoV-2 hosts and presented low ACE2 divergence. A new coronavirus transmission chain was developed in which white-tailed deer, a susceptible SARS-CoV-2 host, have the central position. Cougar play an important role because of its low divergent ACE2 level in deer and humans. The discovery of these potential coronavirus hosts will be useful for epidemiological surveillance and discovery of interventions that can contribute to break the transmission chain.

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Metropolitan Wastewater Analysis for COVID-19 Epidemiological Surveillance

10.1101/2020.04.23.20076679 ◽

2020 ◽

Cited By ~ 10

Author(s):

Walter Randazzo ◽

Enric Cuevas-Ferrando ◽

Rafael Sanjuán ◽

Pilar Domingo-Calap ◽

Gloria Sánchez

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Treatment Cost ◽

Cost Effective ◽

Viral Rna ◽

Epidemiological Surveillance ◽

Effective Strategy ◽

Wastewater Analysis ◽

Efficient Treatment ◽

Containment Measures ◽

Community Transmission

AbstractBackgroundThe COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a rapidly emerging pandemic which has enforced extreme containment measures worldwide. In the absence of a vaccine or efficient treatment, cost-effective epidemiological surveillance strategies are urgently needed.MethodsHere, we have used RT-qPCR for SARS-CoV-2 detection in a series of longitudinal metropolitan wastewaters samples collected during the earliest stages of the epidemic in the Region of Valencia, Spain.ResultsWe were able to consistently detect SARS-CoV-2 RNA in samples taken when communicated cases in that region were only incipient. We also find that the wastewater viral RNA context increased rapidly and anticipated the subsequent ascent in the number of declared cases.InterpretationOur results strongly suggest that the virus was undergoing community transmission earlier than previously believed, and show that wastewater analysis is a sensitive and cost-effective strategy for COVID-19 epidemiological surveillance. Routine implementation of this surveillance tool would significantly improve our preparedness against new or re-occurring viral outbreaks.

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Diabetes mellitus augments the complications of patients with COVID-19: a review

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20202925 ◽

2020 ◽

Vol 8 (7) ◽

pp. 2716

Author(s):

Parthiba Pramanik ◽

Purushottam Pramanik

Keyword(s):

Diabetes Mellitus ◽

Severe Acute Respiratory Syndrome ◽

Virus Disease ◽

Rna Virus ◽

Renin Angiotensin System ◽

Acute Effect ◽

Host Cells ◽

Diabetic Patients ◽

Angiotensin Converting Enzyme 2 ◽

Appropriate Therapy

Corona virus disease 2019 (COVID-19) is current pandemic infection caused by RNA virus named severe acute respiratory syndrome coronavirus-2 (SARS Cov-2). The lungs are the organs most affected by COVID-19 and people were died due to severe acute respiratory s syndrome, pneumonia and multi-organs failure. Fatality rate was more, those who suffer in chronic diseases including diabetes mellitus (DM). As COVID-19 pandemic is accelerating , it is important to understand the molecular mechanism through which DM increases the severity related to COVID-19 to able to design more appropriate therapy. The aims of this study was to identify mechanisms through re-analysis of publicly available data by which DM increases susceptibility for COVID-19 infection and/or increase complication for SARS-Cov-2 infection. SARS Cov-2 accesses host cells via membrane bound enzyme, angiotensin converting enzyme-2 (ACE2). This leads to imbalance of vasoprotective and vasodeletorious arms of renin angiotensin system (RAS) with over activity of vasodeletorious arms. Such imbalance of RAS induces alveolar damage, flooding the alveoli and difficulty in breathing. DM augmented the chance of pulmonary infection by impairment of innate immunity and down regulation of ACE2. Hence, diabetic patients of COVID-19 die from multi-organ failure, shock, heart failure, arrhythmias and renal failure along with severe acute respiratory syndrome. Thus it is concluded that DM augments the complications from COVID-19 by enhancing development of RAS imbalance. From view point of public health it is suggested to keep the lung healthy, maintain blood glucose level properly, and intake foods rich in antioxidant and anti-inflammatory agents to prevent and ameliorate the acute effect of COVID-19 in diabetic patients.

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Role of Endolysosomes in Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Coronavirus Disease 2019 Pathogenesis: Implications for Potential Treatments

Frontiers in Pharmacology ◽

10.3389/fphar.2020.595888 ◽

2020 ◽

Vol 11 ◽

Author(s):

Nabab Khan ◽

Xuesong Chen ◽

Jonathan D. Geiger

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Rna Virus ◽

Therapeutic Strategies ◽

Host Protein ◽

Focus Attention ◽

Angiotensin Converting Enzyme 2 ◽

Immunological Responses ◽

Endocytic Machinery ◽

Replication Sites

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an enveloped, single-stranded RNA virus. Humans infected with SARS-CoV-2 develop a disease known as coronavirus disease 2019 (COVID-19) with symptoms and consequences including acute respiratory distress syndrome (ARDS), cardiovascular disorders, and death. SARS-CoV-2 appears to infect cells by first binding viral spike proteins with host protein angiotensin-converting enzyme 2 (ACE2) receptors; the virus is endocytosed following priming by transmembrane protease serine 2 (TMPRSS2). The process of virus entry into endosomes and its release from endolysosomes are key features of enveloped viruses. Thus, it is important to focus attention on the role of endolysosomes in SARS-CoV-2 infection. Indeed, coronaviruses are now known to hijack endocytic machinery to enter cells such that they can deliver their genome at replication sites without initiating host detection and immunological responses. Hence, endolysosomes might be good targets for developing therapeutic strategies against coronaviruses. Here, we focus attention on the involvement of endolysosomes in SARS-CoV-2 infection and COVID-19 pathogenesis. Further, we explore endolysosome-based therapeutic strategies to restrict SARS-CoV-2 infection and COVID-19 pathogenesis.

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Emerging Strains Of SARS-Cov2 And Their Inhibition by The Use of Phytochemicals: An In-Silico Analysis

10.21203/rs.3.rs-523184/v1 ◽

2021 ◽

Author(s):

Mohammad Faheem Khan ◽

Tanveer Ahamad ◽

Waseem Ahmad Ansari ◽

Mohsin Ali Khan ◽

Zaw Ali Khan ◽

...

Keyword(s):

Rna Virus ◽

In Silico Analysis ◽

Open Reading Frames ◽

Host Cells ◽

Structural Proteins ◽

Angiotensin Converting Enzyme 2 ◽

A Genome ◽

Infectivity Rate ◽

Silico Analysis ◽

Prime Target

Abstract Recently identified coronavirus namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded positive-sense RNA virus with a genome of 29.9 kb in size encoding 14 open reading frames (ORFs) and 27 different structural and non-structural proteins. Among the structural proteins, trimeric-shaped spike glycoprotein is responsible for the entry of the SARS-CoV2 genome into host cells by interacting with human angiotensin-converting enzyme 2 (ACE2) receptors that are present on the cell surface with high affinity. Notably, inhibition of spike protein is considered a prime target for the development of drugs against COVID-19. Viruses can mutate, and SARS-CoV-2 is no exception. Since the first whole genome of SARS-CoV2 was published in February 2020, at least 4400 amino acid substitutions and several thousand mutations have been identified to date. As of today, more than 3500 new variants of SARS-CoV2 have been sequenced with a high spreading and infectivity rate which makes the virus more contagious. These new variants have been spread to several countries including United States (US), United Kingdom (UK), Brazil, South Africa, India, and other countries, etc. Therefore, herein, we analysed the new SARS-CoV2 strains, constructed the 3D homology models of Brazil P.1 and Indian B.1.617 variants, and screened them against 100 phytochemicals having previously identified anti-viral activity. Our study revealed that the top three phytochemicals for each of the new strains might serve as potential anti- SARS-CoV-2 agents for further drug discovery and development process to tackle COVID-19.

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Host Cell and SARS-CoV-2-Associated Molecular Structures and Factors as Potential Therapeutic Targets

Cells ◽

10.3390/cells10092427 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2427

Author(s):

Jitendra Kumar Chaudhary ◽

Rohitash Yadav ◽

Pankaj Kumar Chaudhary ◽

Anurag Maurya ◽

Rakesh Roshan ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Clinical Outcome ◽

Host Cell ◽

Rna Virus ◽

Critical Role ◽

Viral Disease ◽

Molecular Structures ◽

Cell Surface Receptor ◽

Structural Proteins ◽

Lectin Receptors

Coronavirus disease 19 (COVID-19) is caused by an enveloped, positive-sense, single-stranded RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the realm Riboviria, order Nidovirales, family Coronaviridae, genus Betacoronavirus and the species Severe acute respiratory syndrome-related coronavirus. This viral disease is characterized by a myriad of varying symptoms, such as pyrexia, cough, hemoptysis, dyspnoea, diarrhea, muscle soreness, dysosmia, lymphopenia and dysgeusia amongst others. The virus mainly infects humans, various other mammals, avian species and some other companion livestock. SARS-CoV-2 cellular entry is primarily accomplished by molecular interaction between the virus’s spike (S) protein and the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), although other host cell-associated receptors/factors, such as neuropilin 1 (NRP-1) and neuropilin 2 (NRP-2), C-type lectin receptors (CLRs), as well as proteases such as TMPRSS2 (transmembrane serine protease 2) and furin, might also play a crucial role in infection, tropism and pathogenesis and clinical outcome. Furthermore, several structural and non-structural proteins of the virus themselves are very critical in determining the clinical outcome following infection. Considering such critical role(s) of the abovementioned host cell receptors, associated proteases/factors and virus structural/non-structural proteins (NSPs), it may be quite prudent to therapeutically target them through a multipronged clinical regimen to combat the disease.

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Regressing SARS-CoV-2 Sewage Measurements Onto COVID-19 Burden in the Population: A Proof-of-Concept for Quantitative Environmental Surveillance

Frontiers in Public Health ◽

10.3389/fpubh.2021.561710 ◽

2022 ◽

Vol 9 ◽

Author(s):

Itay Bar-Or ◽

Karin Yaniv ◽

Marilou Shagan ◽

Eden Ozer ◽

Merav Weil ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Rna Virus ◽

Health Care Systems ◽

Rna Extraction ◽

Warning System ◽

Epidemiological Surveillance ◽

Virus Concentration ◽

Proof Of Concept ◽

Virus Rna ◽

Care Systems

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus, a member of the coronavirus family of respiratory viruses that includes severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East respiratory syndrome (MERS). It has had an acute and dramatic impact on health care systems, economies, and societies of affected countries during the past 8 months. Widespread testing and tracing efforts are being employed in many countries in attempts to contain and mitigate this pandemic. Recent data has indicated that fecal shedding of SARS-CoV-2 is common and that the virus RNA can be detected in wastewater. This indicates that wastewater monitoring may provide a potentially efficient tool for the epidemiological surveillance of SARS-CoV-2 infection in large populations at relevant scales. In particular, this provides important means of (i) estimating the extent of outbreaks and their spatial distributions, based primarily on in-sewer measurements, (ii) managing the early-warning system quantitatively and efficiently, and (iii) verifying disease elimination. Here we report different virus concentration methods using polyethylene glycol (PEG), alum, or filtration techniques as well as different RNA extraction methodologies, providing important insights regarding the detection of SARS-CoV-2 RNA in sewage. Virus RNA particles were detected in wastewater in several geographic locations in Israel. In addition, a correlation of virus RNA concentration to morbidity was detected in Bnei-Barak city during April 2020. This study presents a proof of concept for the use of direct raw sewage-associated virus data, during the pandemic in the country as a potential epidemiological tool.

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Rapid Antibody-Based COVID-19 Mass Surveillance: Relevance, Challenges, and Prospects in a Pandemic and Post-Pandemic World

Journal of Clinical Medicine ◽

10.3390/jcm9103372 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3372 ◽

Cited By ~ 3

Author(s):

Robin Augustine ◽

Suvarthi Das ◽

Anwarul Hasan ◽

Abhilash S ◽

Shaheen Abdul Salam ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Disease Outbreaks ◽

Disease Spread ◽

Host Immune System ◽

Sample Collection ◽

Non Invasive ◽

Testing Tools ◽

Rapid Tests ◽

Economic Tools ◽

Mass Surveillance

The aggressive outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as COVID-19 (coronavirus disease-2019) pandemic demands rapid and simplified testing tools for its effective management. Increased mass testing and surveillance are crucial for controlling the disease spread, obtaining better pandemic statistics, and developing realistic epidemiological models. Despite the advantages of nucleic acid- and antigen-based tests such as accuracy, specificity, and non-invasive approaches of sample collection, they can only detect active infections. Antibodies (immunoglobulins) are produced by the host immune system within a few days after infection and persist in the blood for at least several weeks after infection resolution. Antibody-based tests have provided a substitute and effective method of ultra-rapid detection for multiple contagious disease outbreaks in the past, including viral diseases such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). Thus, although not highly suitable for early diagnosis, antibody-based methods can be utilized to detect past infections hidden in the population, including asymptomatic ones. In an active community spread scenario of a disease that can provide a bigger window for mass detections and a practical approach for continuous surveillance. These factors encouraged researchers to investigate means of improving antibody-based rapid tests and employ them as reliable, reproducible, sensitive, specific, and economic tools for COVID-19 mass testing and surveillance. The development and integration of such immunoglobulin-based tests can transform the pandemic diagnosis by moving the same out of the clinics and laboratories into community testing sites and homes. This review discusses the principle, technology, and strategies being used in antibody-based testing at present. It also underlines the immense prospect of immunoglobulin-based testing and the efficacy of repeated planned deployment in pandemic management and post-pandemic sustainable screenings globally.

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Immunoinformatics-guided design of a multi-epitope vaccine based on the structural proteins of severe acute respiratory syndrome coronavirus 2

RSC Advances ◽

10.1039/d1ra02885e ◽

2021 ◽

Vol 11 (29) ◽

pp. 18103-18121

Author(s):

Ahmad J. Obaidullah ◽

Mohammed M. Alanazi ◽

Nawaf A. Alsaif ◽

Hussam Albassam ◽

Abdulrahman A. Almehizia ◽

...

Keyword(s):

Tract Infection ◽

Severe Acute Respiratory Syndrome ◽

Respiratory Tract ◽

Respiratory Tract Infection ◽

Structural Proteins ◽

Epitope Vaccine

COVID-19 is caused by SARS-CoV-2, resulting in a contagious respiratory tract infection. For designing a multi-epitope vaccine, we utilized the four structural proteins from the SARS-CoV-2 by using bioinformatics and immunoinformatics analysis.

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Structure and Function of Major SARS-CoV-2 and SARS-CoV Proteins

Bioinformatics and Biology Insights ◽

10.1177/11779322211025876 ◽

2021 ◽

Vol 15 ◽

pp. 117793222110258

Author(s):

Ritesh Gorkhali ◽

Prashanna Koirala ◽

Sadikshya Rijal ◽

Ashmita Mainali ◽

Adesh Baral ◽

...

Keyword(s):

Genomic Organization ◽

Membrane Vesicles ◽

Structural Proteins ◽

Host Immune System ◽

Accessory Proteins ◽

Nonstructural Proteins ◽

N Protein ◽

Small Proteins ◽

Methylation Mark ◽

And Function

SARS-CoV-2 virus, the causative agent of COVID-19 pandemic, has a genomic organization consisting of 16 nonstructural proteins (nsps), 4 structural proteins, and 9 accessory proteins. Relative of SARS-CoV-2, SARS-CoV, has genomic organization, which is very similar. In this article, the function and structure of the proteins of SARS-CoV-2 and SARS-CoV are described in great detail. The nsps are expressed as a single or two polyproteins, which are then cleaved into individual proteins using two proteases of the virus, a chymotrypsin-like protease and a papain-like protease. The released proteins serve as centers of virus replication and transcription. Some of these nsps modulate the host’s translation and immune systems, while others help the virus evade the host immune system. Some of the nsps help form replication-transcription complex at double-membrane vesicles. Others, including one RNA-dependent RNA polymerase and one exonuclease, help in the polymerization of newly synthesized RNA of the virus and help minimize the mutation rate by proofreading. After synthesis of the viral RNA, it gets capped. The capping consists of adding GMP and a methylation mark, called cap 0 and additionally adding a methyl group to the terminal ribose called cap1. Capping is accomplished with the help of a helicase, which also helps remove a phosphate, two methyltransferases, and a scaffolding factor. Among the structural proteins, S protein forms the receptor of the virus, which latches on the angiotensin-converting enzyme 2 receptor of the host and N protein binds and protects the genomic RNA of the virus. The accessory proteins found in these viruses are small proteins with immune modulatory roles. Besides functions of these proteins, solved X-ray and cryogenic electron microscopy structures related to the function of the proteins along with comparisons to other coronavirus homologs have been described in the article. Finally, the rate of mutation of SARS-CoV-2 residues of the proteome during the 2020 pandemic has been described. Some proteins are mutated more often than other proteins, but the significance of these mutation rates is not fully understood.

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