Scientific research progress of COVID‐19/SARS‐CoV‐2 in the first five months

A cluster of pneumonia (COVID‐19) cases have been found in Wuhan China in late December, 2019, and subsequently, a novel coronavirus with a positive stranded RNA was identified to be the aetiological virus (severe acute respiratory syndrome coronavirus 2, SARS‐CoV‐2), which has a phylogenetic similarity to severe acute respiratory syndrome coronavirus (SARS‐CoV). SARS‐CoV‐2 transmits mainly through droplets and close contact and the elder or people with chronic diseases are high‐risk population. People affected by SARS‐CoV‐2 can be asymptomatic, which brings about more difficulties to control the transmission. COVID‐19 has become pandemic rapidly after onset, and so far the infected people have been above 2 000 000 and more than 130 000 died worldwide according to COVID‐19 situation dashboard of World Health Organization ( https://covid19.who.int ). Here, we summarized the current known knowledge regarding epidemiological, pathogenesis, pathology, clinical features, comorbidities and treatment of COVID‐19/ SARS‐CoV‐2 as reference for the prevention and control COVID‐19.     

A five‐step risk management process for geriatric dental practice during SARS‐CoV‐2 pandemic

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an RNA virus that causes coronavirus infection (COVID‐19). COVID‐19 is a highly contagious disease transmitted through respiratory droplets, saliva and other contact routes. Within 10 months of its outbreak, SARS‐CoV‐2 has infected more than 23 million people around the world. Evidence suggests that older adults are the most vulnerable to infection and have an increased risk of mortality. Reduced immunity and underlying medical conditions make them risk‐prone and vulnerable to critical care. Older adults affected with the SARS‐CoV‐2 virus present with distinct clinical manifestations necessitating specific treatment needs and management protocols. While it is crucial to prevent the spread of novel coronavirus (2019‐nCoV), the role of oral healthcare workers in addressing the specific needs of ageing adult patients by adopting specific guidelines and appropriate infection control protocols is timely. This paper aims to develop specific guidelines and protocols for the dental management of geriatric patients during the COVID‐19 pandemic.     

The potential effects of DPP‐4 inhibitors on cardiovascular system in COVID‐19 patients

With the outbreak of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the public healthcare systems are facing great challenges. Coronavirus disease 2019 (COVID‐19) could develop into severe pneumonia, acute respiratory distress syndrome and multi‐organ failure. Remarkably, in addition to the respiratory symptoms, some COVID‐19 patients also suffer from cardiovascular injuries. Dipeptidyl peptidase‐4 (DPP‐4) is a ubiquitous glycoprotein which could act both as a cell membrane‐bound protein and a soluble enzymatic protein after cleavage and release into the circulation. Despite angiotensin‐converting enzyme 2 (ACE2), the recently recognized receptor of SARS‐CoV and SARS‐CoV‐2, which facilitated their entries into the host, DPP‐4 has been identified as the receptor of middle east respiratory syndrome coronavirus (MERS‐CoV). In the current review, we discussed the potential roles of DPP‐4 in COVID‐19 and the possible effects of DPP‐4 inhibitors on cardiovascular system in patients with COVID‐19.     

The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS‐CoV‐2 infection

The serious coronavirus disease‐2019 (COVID‐19) was first reported in December 2019 in Wuhan, China. COVID‐19 is an infectious disease caused by severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Angiotensin converting enzyme 2(ACE2) is the cellular receptor for SARS‐CoV‐2. Considering the critical roles of testicular cells for the transmission of genetic information between generations, we analyzed single‐cell RNA‐sequencing (scRNA‐seq) data of adult human testis. The mRNA expression of ACE2 was expressed in both germ cells and somatic cells. Moreover, the positive rate of ACE2 in testes of infertile men was higher than normal, which indicates that SARS‐CoV‐2 may cause reproductive disorders through pathway activated by ACE2 and the men with reproductive disorder may easily to be infected by SARS‐CoV‐2. The expression level of ACE2 was related to the age, and the mid‐aged with higher positive rate than young men testicular cells. Taken together, this research provides a biological background of the potential route for infection of SARS‐CoV‐2 and may enable rapid deciphering male‐related reproductive disorders induced by COVID‐19.     

Molecular Targets for the Testing of COVID‐19

The pandemic outbreaks of coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), spread all over the world in a short period of time. Efficient identification of the infection by SARS‐CoV‐2 has been one of the most important tasks to facilitate all the following counter measurements in dealing with the infectious disease. In Taiwan, a COVID‐19 Open Science Platform adheres to the spirit of open science: sharing sources, data, and methods to promote progress in academic research while corroborating findings from various disciplines has established in mid‐February 2020, for collaborative research in support of the development of detection methods, therapeutics, and a vaccine for COVID‐19. Research priorities include infection control, epidemiology, clinical characterization and management, detection methods (including viral RNA detection, viral antigen detection, and serum antibody detection), therapeutics (neutralizing antibody and small molecule drugs), vaccines, and SARS‐CoV‐2 pathogenesis. In addition, research on social ethics and the law are included to take full account of the impact of the COVID‐19 virus.     

Systematic profiling of ACE2 expression in diverse physiological and pathological conditions for COVID‐19/SARS‐CoV‐2

Recent retrospective studies of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) disease (COVID‐19) revealed that the patients with common comorbidities of cancers and chronic diseases face significantly poorer clinical outcomes than those without. Since the expression profile of ACE2, a crucial cell entry receptor for SARS‐CoV‐2, could indicate the susceptibility to SARS‐CoV‐2 infection, here we systematically dissected ACE2 expression using large‐scale multi‐omics data from 30 organs/tissues, 33 cancer types and some common chronic diseases involving >28 000 samples. It was found that sex and age could be correlated with the susceptibility of SARS‐CoV‐2 infection for certain tissues. Strikingly, ACE2 was up‐regulated in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, oesophageal carcinoma, kidney renal papillary cell carcinoma, lung adenocarcinoma and uterine corpus endometrial carcinoma compared to controls. Furthermore, the patients with common chronic diseases regarding angiocardiopathy, type 2 diabetes, liver, pneumonia and hypertension were also with higher ACE2 expression compared to related controls, which were validated using independent data sets. Collectively, our study may reveal a novel important mechanism that the patients with certain cancers and chronic diseases may express higher ACE2 expression compared to the individuals without diseases, which could lead to their higher susceptibility to multi‐organ injury of SARS‐CoV‐2 infection.     

Proteomics in the COVID‐19 Battlefield: First Semester Check‐Up

Proteomics offers a wide collection of methodologies to study biological systems at the finest granularity. Faced with COVID‐19, the most worrying pandemic in a century, proteomics researchers have made significant progress in understanding how the causative virus hijacks the host's cellular machinery and multiplies exponentially, how the disease can be diagnosed, and how it develops, as well as its severity predicted. Numerous cellular targets of potential interest for the development of new antiviral drugs have been documented. Here, the most striking results obtained in the proteomics field over this first semester of the pandemic are presented. The molecular machinery of SARS‐CoV‐2 is much more complex than initially believed, as many post‐translational modifications can occur, leading to a myriad of proteoforms and a broad heterogeneity of viral particles. The interplay of protein–protein interactions, protein abundances, and post‐translational modifications has yet to be fully documented to provide a full picture of this intriguing but lethal biological threat. Proteomics has the potential to provide rapid detection of the SARS‐CoV‐2 virus by mass spectrometry proteotyping, and to further increase the knowledge of severe respiratory syndrome COVID‐19 and its long‐term health consequences.     

Susceptibility to COVID‐19 in populations with health disparities: Posited involvement of mitochondrial disorder,socioeconomic stress,and pollutants

SARS‐CoV‐2 is a novel betacoronavirus that has caused the global health crisis known as COVID‐19. The implications of mitochondrial dysfunction with COVID‐19 are discussed as well as deregulated mitochondria and inter‐organelle functions as a posited comorbidity enhancing detrimental outcomes. Many environmental chemicals (ECs) and endocrine‐disrupting chemicals can do damage to mitochondria and cause mitochondrial dysfunction. During infection, SARS‐CoV‐2 via its binding target ACE2 and TMPRSS2 can disrupt mitochondrial function. Viral genomic RNA and structural proteins may also affect the normal function of the mitochondria‐endoplasmic reticulum‐Golgi apparatus. Drugs considered for treatment of COVID‐19 should consider effects on organelles including mitochondria functions. Mitochondrial self‐balance and clearance via mitophagy are important in SARS‐CoV‐2 infection, which indicate monitoring and protection of mitochondria against SARS‐CoV‐2 are important. Mitochondrial metabolomic analysis may provide new indicators of COVID‐19 prognosis. A better understanding of the role of mitochondria during SARS‐CoV‐2 infection may help to improve intervention therapies and better protect mitochondrial disease patients from pathogens as well as people living with poor nutrition and elevated levels of socioeconomic stress and ECs.     

Shortlisting SARS‐CoV‐2 Peptides for Targeted Studies from Experimental Data‐Dependent Acquisition Tandem Mass Spectrometry Data

Detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a crucial tool for fighting the COVID‐19 pandemic. This dataset brief presents the exploration of a shotgun proteomics dataset acquired on SARS‐CoV‐2 infected Vero cells. Proteins from inactivated virus samples were extracted, digested with trypsin, and the resulting peptides were identified by data‐dependent acquisition tandem mass spectrometry. The 101 peptides reporting for six viral proteins were specifically analyzed in terms of their analytical characteristics, species specificity and conservation, and their proneness to structural modifications. Based on these results, a shortlist of 14 peptides from the N, S, and M main structural proteins that could be used for targeted mass‐spectrometry method development and diagnostic of the new SARS‐CoV‐2 is proposed and the best candidates are commented.     

COVID‐19 and olfactory dysfunction: A possible associative approach towards neurodegenerative diseases

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the agent of novel coronavirus 2019 (COVID‐19), has kept the globe in disquiets due to its severe life‐threatening conditions. The most common symptoms of COVID‐19 are fever, sore throat, and shortness of breath. According to the anecdotal reports from the health care workers, it has been suggested that the virus could reach the brain and can cause anosmia, hyposmia, hypogeusia, and hypopsia. Once the SARS‐CoV‐2 has entered the central nervous system (CNS), it can either exit in an inactive form in the tissues or may lead to neuroinflammation. Here, we aim to discuss the chronic infection of the olfactory bulb region of the brain by SARS‐CoV‐2 and how this could affect the nearby residing neurons in the host. We further review the probable cellular mechanism and activation of the microglia 1 phenotype possibly leading to various neurodegenerative disorders. In conclusion, SARS‐CoV‐2 might probably infect the olfactory bulb neuron enervating the nasal epithelium accessing the CNS and might cause neurodegenerative diseases in the future.     

Is there a link between vitamin D status,SARS‐CoV‐2 infection risk and COVID‐19 severity?

The outbreak of COVID‐19 emerged in December 2019 rapidly spread across the globe and has become pandemic. Little is known about the protective factors of this infection, which is equally distributed between genders and different ages while severe and poor prognosis cases are strongly associated to old males and the presence of comorbidities. Thus, preventive measures aiming at reducing the number of infection and/or their severity are strongly needed. Vitamin D has got great attention and has been claimed as potentially protective against the infection since it may be associated with immunocompetence, inflammation, aging, and those diseases involved in determining the outcomes of COVID‐19. This narrative review aims at collecting the literature available on the involvement of the vitamin D status in the pathogenesis of COVID‐19 and the putative utility of vitamin D supplementation in the therapeutics. It emerges that a poor vitamin D status seems to associate with an increased risk of infection whereas age, gender and comorbidities seem to play a more important role in COVID‐19 severity and mortality. While randomized control trials are needed to better inquire into this topic, vitamin D supplementation may be useful beside its potential effects on SARS‐CoV‐2 infection and COVID‐19.     

Predicting susceptibility for SARS‐CoV‐2 infection in domestic and wildlife animals using ACE2 protein sequence homology

The article is presenting a bioinformatics based method predicting susceptibility for SARS‐CoV‐2 infection in domestic and wildlife animals. Recently, there were reports of cats and ferrets, dogs, minks, golden hamster, rhesus monkeys, tigers, and lions testing for SARS‐CoV‐2 RNA which indicated for the possible interspecies viral transmission. Our method successfully predicted the susceptibility of these animals for contracting SARS‐CoV‐2 infection. This method can be used as a screening tool for guiding viral RNA testing for domestic and wildlife animals at risk of getting COVID‐19. We provide a list of the animals at risk of developing COVID‐19 based on the susceptibility score.     

Does High Cardiorespiratory Fitness Confer Some Protection Against Proinflammatory Responses After Infection by SARS‐CoV‐2?

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) originated in China in late 2019 and has since spread rapidly to every continent in the world. This pandemic continues to cause widespread personal suffering, along with severe pressure on medical and health care providers. The symptoms of SARS‐CoV‐2 and the subsequent prognosis are worsened in individuals who have preexisting comorbidities prior to infection by the virus. Individuals with obesity or overweight, insulin resistance, and diabetes typically have chronic low‐grade inflammation characterized by increased levels of several proinflammatory cytokines and the inflammasome; this state predisposes to greater risk for infection along with more adverse outcomes. Here, we consider whether a high level of cardiorespiratory fitness induced by prior exercise training may confer some innate immune protection against COVID‐19 by attenuating the “cytokine storm syndrome” often experienced by “at risk” individuals.     

Covid‐19.bioreproducibility.org: A web resource for SARS‐CoV‐2‐related structural models

The COVID‐19 pandemic has triggered numerous scientific activities aimed at understanding the SARS‐CoV‐2 virus and ultimately developing treatments. Structural biologists have already determined hundreds of experimental X‐ray, cryo‐EM, and NMR structures of proteins and nucleic acids related to this coronavirus, and this number is still growing. To help biomedical researchers, who may not necessarily be experts in structural biology, navigate through the flood of structural models, we have created an online resource, covid19.bioreproducibility.org, that aggregates expert‐verified information about SARS‐CoV‐2‐related macromolecular models. In this article, we describe this web resource along with the suite of tools and methodologies used for assessing the structures presented therein.     

Lessons from the Ebola epidemics and their applications for COVID‐19 pandemic response in sub‐Saharan Africa

COVID‐19, caused by a novel coronavirus named SARS‐CoV‐2, was identified in December 2019, in Wuhan, China. It was first confirmed in sub‐Saharan Africa in Nigeria on 27 February 2020 and has since spread quickly to all sub‐Saharan African countries, causing more than 111,309 confirmed cases and 2,498 deaths as of 03 June 2020. The lessons learned during the recent Ebola virus disease (EVD) outbreaks in some sub‐Saharan African countries were expected to shape and influence the region’s responses to COVID‐19 pandemic. However, some of the challenges associated with the management of the EVD outbreaks persist and create obstacles for the effective management of the COVID‐19 pandemic. This article describes the commonalities between the EVD epidemics and COVID‐19 pandemic, with a view to draw on lessons learned to effectively tackle the ongoing pandemic. Key successes, failures and lessons learned from previous EVD outbreaks are discussed. Recommendations on how these lessons can be translated to strengthen the COVID‐19 response in sub‐Saharan Africa are provided.     

Architecture and self‐assembly of the SARS‐CoV‐2 nucleocapsid protein

The COVID‐2019 pandemic is the most severe acute public health threat of the twenty‐first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS‐CoV‐2 coronavirus. Here, we examine the architecture and self‐assembly properties of the SARS‐CoV‐2 nucleocapsid protein, which packages viral RNA into new virions. We determined a 1.4 Å resolution crystal structure of this protein's N2b domain, revealing a compact, intertwined dimer similar to that of related coronaviruses including SARS‐CoV. While the N2b domain forms a dimer in solution, addition of the C‐terminal spacer B/N3 domain mediates formation of a homotetramer. Using hydrogen‐deuterium exchange mass spectrometry, we find evidence that at least part of this putatively disordered domain is structured, potentially forming an α‐helix that self‐associates and cooperates with the N2b domain to mediate tetramer formation. Finally, we map the locations of amino acid substitutions in the N protein from over 38,000 SARS‐CoV‐2 genome sequences. We find that these substitutions are strongly clustered in the protein's N2a linker domain, and that substitutions within the N1b and N2b domains cluster away from their functional RNA binding and dimerization interfaces. Overall, this work reveals the architecture and self‐assembly properties of a key protein in the SARS‐CoV‐2 life cycle, with implications for both drug design and antibody‐based testing.     

Comparing the binding properties of peptides mimicking the Envelope protein of SARS‐CoV and SARS‐CoV‐2 to the PDZ domain of the tight junction‐associated PALS1 protein

The Envelope protein (E) is one of the four structural proteins encoded by the genome of SARS‐CoV and SARS‐CoV‐2 Coronaviruses. It is an integral membrane protein, highly expressed in the host cell, which is known to have an important role in Coronaviruses maturation, assembly and virulence. The E protein presents a PDZ‐binding motif at its C‐terminus. One of the key interactors of the E protein in the intracellular environment is the PDZ containing protein PALS1. This interaction is known to play a key role in the SARS‐CoV pathology and suspected to affect the integrity of the lung epithelia. In this paper we measured and compared the affinity of peptides mimicking the E protein from SARS‐CoV and SARS‐CoV‐2 for the PDZ domain of PALS1, through equilibrium and kinetic binding experiments. Our results support the hypothesis that the increased virulence of SARS‐CoV‐2 compared to SARS‐CoV may rely on the increased affinity of its Envelope protein for PALS1.     

Influence of hydrophobic and electrostatic residues on SARS‐coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design

Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by the SARS‐coronavirus (SARS‐CoV). SARS‐CoV entry is facilitated by the spike protein (S), which consists of an N‐terminal domain (S1) responsible for cellular attachment and a C‐terminal domain (S2) that mediates viral and host cell membrane fusion. The SARS‐CoV S2 is a potential drug target, as peptidomimetics against S2 act as potent fusion inhibitors. In this study, site‐directed mutagenesis and thermal stability experiments on electrostatic, hydrophobic, and polar residues to dissect their roles in stabilizing the S2 postfusion conformation was performed. It was shown that unlike the pH‐independent retroviral fusion proteins, SARS‐CoV S2 is stable over a wide pH range, supporting its ability to fuse at both the plasma membrane and endosome. A comprehensive SARS‐CoV S2 analysis showed that specific hydrophobic positions at the C‐terminal end of the HR2, rather than electrostatics are critical for fusion protein stabilization. Disruption of the conserved C‐terminal hydrophobic residues destabilized the fusion core and reduced the melting temperature by 30°C. The importance of the C‐terminal hydrophobic residues led us to identify a 42‐residue substructure on the central core that is structurally conserved in all existing CoV S2 fusion proteins (root mean squared deviation = 0.4 Å). This is the first study to identify such a conserved substructure and likely represents a common foundation to facilitate viral fusion. We have discussed the role of key residues in the design of fusion inhibitors and the potential of the substructure as a general target for the development of novel therapeutics against CoV infections.