A Comparative Study of SARS, MERS with COVID-19

Background: B814, now's called Coronavirus first identified by Tyrrell and Bynoe in 1965 from the respiratory tract (embryonic tracheal) of an adult and later on during working on National Institutes of Health Robert Chanock used the term "OC" for same virus strain. After several years researchers reported that coronaviruses were caused disease in rats, mice, chickens, turkeys, calves, dogs, cats, rabbits etc. after effecting the enormous variety of animal, in year 2002-2003 it caused new respiratory disease named severe acute respiratory syndrome, (SARS) in southern China. Objective(s): The main objective of this article is to compare the status of various previous pandemics (i.e., SARS, MERS) with the current COVID-19 pandemic in terms of the life cycle, diagnosis process and prevention Results: On 31st December 2019, the World Health Organization (WHO) office in China received information regarding pneumonia cases of unknown etiology from the Wuhan district in central China. Subsequently, this new disease spread to China, and from there, to the rest of the world. By the end of March 2020, more than 2 million cases were confirmed of this new disease, with over 70000 deaths worldwide. After some time, researchers have identified that this new disease is caused by a novel beta-Coronavirus (virus SARS-CoV-2) and the new disease was named COVID-19. Since then, the Ministry of Health of various countries and WHO have been fighting this health emergency, which has not only affected public health, but also affected various economic sectors. Conclusion(s): The current outbreak SARS-CoV-2 phylogenetically resembled to Bat SARS, which was previously identified in year 2002 and 2012 having low mortality rate than MERS and SARS. However, SARS-CoV-2 and MERS having high virological similarity but both use different receptors to take entry in to the host cell via ACE-2 and DPP-4 respectively. Unfortunately, currently there is no approved treatment available worldwide. Currently, we can hope that together we will recover from this public health emergency very soon.Copyright © 2021 Bentham Science Publishers.

COVID-19: Insights into Structure-Function Relationship, Drug Targets and Drug Design Strategies for Novel-Coronavirus 2019

Background: Novel coronavirus (2019-nCov) imposed deadly health calamity with unexpected disastrous situation alarming the globe for urgent treatment regimes. World Health Organization (WHO) termed the coronavirus disease as COVID-2019 on February 11, 2020 and announced its outbreak as pandemic on 11 March 2020. The first infection was noticed in Wuhan, Hubei province, China, in December 2019, and it is believed that the corona-virus is transmitted to humans through bats as a reservoir involving human to human transfer. However, the proper intermediary transmission channel is yet to be unestablished. Method(s): Elderly populations and patients with concomitant symptoms are more at risk as compared to middle-aged patients as it may progress to pneumonia followed by severe acute respiratory syndrome (SARS) and multi-organ failure. Morbidity rates estimated in patients are less, i.e., 2-3%, but the dearth of a specific treatment strategy to prevent coronavirus infection is a major concern. Result(s): Currently, anti-viral and anti-malarial drugs are in practice for the management of COVID-19 disease along with plasma therapy in the absence of a potent vaccine. Besides, home isolation and social distancing are the precautionary measures adopted by many countries to minimize the spread of infection. Various studies have been conducted, and numerous are still going on to establish specific treatment for COVID-19. Conclusion(s): In this review, we summarized information on the structural components of COVID19 virus with special emphasis on the virus genome, life cycle, the importance of protease enzyme, the role of spike proteins in viral replication, validated drug targets, ongoing effective treatments for COVID-19 management and the latest research on drug design to develop anti-CoV drugs.Copyright © 2021 Bentham Science Publishers.

Chemoinformatics and bioinformatics by discrete mathematics and numbers: an adventure from small data to the realm of emerging big data

Currently, we are witnessing the emergence of big data in various fields including the biomedical and natural sciences. The size of chemoinformatics and bioinformatics databases is increasing every day. This gives us both challenges and opportunities. This chapter discusses the mathematical methods used in these fields both for the generation and analysis of such data. It is emphasized that proper use of robust statistical and machine learning methods in the analysis of the available big data may facilitate both hypothesis-driven and discovery-oriented research. © 2023 Elsevier Inc. All rights reserved.

Repositioning of Drugs as a Promising Strategy to Fight COVID-19

Background and Objective: With the initial case of corona reported in Wuhan, China on 31st December 2020, there has been an unprecedented rise in the coronavirus disease (COVID-19), with over 200 countries all across the world in less than 3 months. By the October 2020, about 40 million population of the world got infected and over one million deaths occurred. Since no WHO and FDA approved medications or vaccines for COVID-19 were available, there was an impatient bustling need to develop a drug for the treatment. Drug repurposing emerged as the easiest and fast emerging strategy to get medicine for COVID-19 with rapid approvals for the clinical trials. The purpose of this study was to evaluate the status of drug repurposing under the clinical and its impact on the development of medicine for COVID-19. Method(s): The study was undertaken to review various clinical trials from the website. www.clinicaltrials.gov. We evaluated 220 ongoing clinical trials with the strategy of 'drug repur-posing' against COVID-19, analyzed them as per their chemical structure and possible biological targets. Result(s): It was noticed that some of the early repurposed drugs like chloroquine, hydroxychloro-quine, ACE inhibitors and ARBs, did not succeed and remained controversial. While many of the antiviral drugs like remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir could be taken for the clinical trials in various countries, remdesivir could succeed to a great extent as compared to other drugs. WHO has come up with an initiative known as multi-country 'Solidarity Trial' for developing a potential drug or therapy against COVID-19.However, the most preferred drugs used for re-purposing like hydroxychloroquine and remdesivir have not shown predictable results in solidarity trials. Conclusion(s): The analyses of several ongoing and partially concluded clinical trials suggest that drug repurposing can be one of the major strategies for the treatment of COVID-19. Further, guidelines framed by the WHO through Infection Prevention and Control for monitoring the widespread of this COVID-19 across the world is another aggressive attempt to find the solution for the treatment for COVID-19.Copyright © 2021 Bentham Science Publishers.

Antiviral Effects of Asian Natural Products Targeting SARS, MERS, and COVID-19

Viral diseases initiated by Coronavirus (CoV) have become the major public health problems worldwide in the last two decades. The recent emergence of the deadly COVID-19 due to SARS-CoV-2 has created unprecedented pandemic situations around the globe making the need for antiviral molecules to treat it. Encountering the health conditions of the patients with synthetic molecules has shown some unpredictable results, including side effects. To face this complex situa-tion, natural products can be good sources of enormous treatment options with fewer side effects. Wide diversity, easy availability, and a good number of scientific researches on Asian origin natural products can be a great tool to meet this critical situation. This paper reviews the currently available Asian natural products with potential antiviral effects on CoV. It includes the potential natural products of whole plant extract, partial plant extract, isolated pure compounds, and isolated pure set of compounds. Besides, the available information of in vitro and in silico from very recent pa-pers are also summarized for the ease of future research. As a rapid search for a potential anti-CoV therapy is undergoing, Asian natural products will provide promising results but still, there are many challenges in front of us, including the robust in vitro assay to confirm the antiviral property, toxicity analysis, and fulfillment of regulatory needs. The use of appropriate natural products with the potential for a safe and more effective anti-CoV property requires multidisciplinary research with preclinical and clinical researchers, which will improve their clinical applications.Copyright © 2021 Bentham Science Publishers.

Mental health in biological disasters: From SARS to COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19), like severe acute respiratory syndrome (SARS), provokes fear, anxiety and depression in the public, which further affects mental health issues. Taiwan has used their experience of the SARS epidemic for the management of foreseeable problems in COVID-19 endemic. AIM/OBJECTIVE: This review summarizes issues concerning mental health problems related to infectious diseases from current literatures. RESULTS: In suspected cases under quarantine, confirmed cases in isolation and their families, health care professionals, and the general population and related effective strategies to reduce these mental health issues, such as helping to identify stressors and normalizing their impact at all levels of response as well as public information and communication messages by electronic devices. The importance of community resilience was also addressed. Psychological first aid, psychological debriefing, mental health intervention and psychoeducation were also discussed. Issues concerning cultures and religions are also emphasized in the management plans. CONCLUSION: Biological disaster like SARS and COVID-19 not only has strong impact on mental health in those being infected and their family, friends, and coworkers, but also affect wellbeing in general public. There are evidenced that clear and timely psychoeducation, psychological first aid and psychological debriefing could amileorate negative impact of disaster, thus might also be helpful amid COVID-19 pandemic.

The Significance of Angiotensin-Converting Enzyme-2 (ACE2) in SARS-Cov-2 Infection and COVID-19

The new coronavirus was first reported in 2019 (China) and officially announced by the World Health Organization as a pandemic in March 2020. Severe acute respiratory syndrome coro-navirus 2 (SARS-CoV-2) is the causative agent of the pneumonia-associated illnesses and shares structural homology with the related Severe acute respiratory syndrome coronavirus-1 (SARS-CoV--1). One of the mechanisms for SARS-Cov-1 and-2 infection is mediated by the angiotensin-con-verting enzyme-2 (ACE2) cell receptor, enabling the virus to enter the host cells. ACE2 is an iso-form of the angiotensin-converting enzyme 1 (ACE). The actions of ACE2 counterbalance the clas-sic renin-angiotensin system (RAS) axis through the production of Ang 1-7, which promotes car-diovascular, renal, and lung-protective effects. The ACE2 is not the only route for SARS-CoV-2 to enter the host cells. However, due to its roles in the RAS and its participation in the SARS-CoV-2 virulence, ACE2 has gained attention regarding viral mechanisms of pathogenesis, effects of drugs that interfere with the RAS, and as a potential target for therapeutic strategies for the damages caused by SARS-CoV-2 infection. Among other tissues, ACE2 gene expression seems to be in-creased in the lungs upon SARS-CoV-2 infection;however, amid other variables, expression and/or activity of ACE2 is shown as a disease, sex, and age-dependent. The present review covers critical aspects for a comprehensive understanding of ACE2 and its current involvement in SARS-CoV-2 infection and the development of COVID-19.Copyright © 2021 Bentham Science Publishers.

Immunisation against COVID-19 in Pregnancy and of Women Planning Pregnancy.

Following reports of the first human SARS-CoV2 infection in December 2019 from Wuhan Province, China, there was such rapid spread that by March 2021, the World Health Organization (WHO) had declared a pandemic. Over 6.5 million people have died from this infection worldwide, although this is most likely an underestimate. Until vaccines became available, mortality and severe morbidity were costly in terms of life lost as well as the cost of supporting the severely and acutely ill. Vaccination changed the landscape, and following worldwide adoption, life has gradually been returning to normal. The speed of production of the vaccines was unprecedented and undoubtedly ushered in a new era in the science of fighting infections. The developed vaccines were on the already known platforms for vaccine delivery: inactivated virus, virus vector, virus-like particles (VLP) subunit, DNA and mRNA. The mRNA platform was used for the first time to deliver vaccines to humans. An understanding of these platforms and the pros and cons of each are important for clinicians who are often challenged by the recipients on the advantages and risks of these vaccines. These vaccines have so far and reassuringly been shown to be safe in reproduction (with no effect on gametes) and pregnancy (not associated with congenital malformations). However, safety remains paramount and continuing vigilance is critical, especially against rare fatal complications such as vaccine-induced thrombocytopenia and myocarditis. Finally, the waning immunity months after vaccination means repeated immunisation is likely to be ongoing, but just how often and how many such revaccinations should be recommended remains uncertain. Research into other vaccines and alternate delivery methods should continue as this infection is likely to be around for a long time.

Human Coronavirus Infections—Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and SARS-CoV-2

Three novel coronaviruses have emerged as new lethal zoonotic pathogens of humans during the past 17 years: The Severe Acute Respiratory Syndrome (SARS) coronavirus (SARS-CoV), the Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV), and most recently SARS-CoV-2. SARS-CoV first surfaced as a human pathogen in Guangdong, China in November 2002 and rapidly spread worldwide with 8098 cases and 774 deaths before the end of the epidemic. SARS-like CoVs have been detected in horseshoe bats with high sequence homology with human or civet isolates, suggesting that bats could be a natural reservoir of a close ancestor of SARS-CoV. No cases of SARS have been reported since January 2004. MERS-CoV was first reported in September 2012, after it was isolated from respiratory samples from a patient in Jeddah, Saudi Arabia who died in June 2012. How humans acquire MERS-CoV infection is not yet known although bats and dromedary camels are intermediary reservoirs. MERS-CoV continues to circulate in the Middle East. As of May 22, 2019, 2428 cases of laboratory-confirmed MERS-CoV cases reported to the World Health Organization, including 838 deaths (34.5% mortality) have been reported from 27 countries. While the majority of MERS cases occur in the Middle East, travel related MERS cases have been reported from all continents. Large health care associated outbreaks of MERS-CoV have occurred in Saudi Arabia, United Arab Emirates, and the Republic of Korea. SARS-CoV-2 emerged from Wuhan, China in December 2019, and by March 2020 had established as a pandemic which has caused massive disruption in multiple countries. The eventual mortality caused by this virus remains to be seen. All three viruses cause a similar wide range of nonspecific clinical manifestations from mild upper respiratory tract illness to severe respiratory, gastrointestinal and other extra-pulmonary disease. Early recognition of cases, improved compliance with internationally recommended infection control protocols, and rapid implementation of infection control measures are required to prevent health care facility-associated outbreaks, and in the case of SARS-CoV-2 for control of community spread as well. Treatment is supportive and there are no specific antivirals or vaccines available for both SARS and MERS. © 2022 Elsevier Ltd. All rights reserved

Covid 19 Pandemic: An Overview

In the 1930's the corona virus was first identified as a highly contagious chicken respiratory virus. Two human coronaviruses were later identified, the human coronavirus 229E causing the flu and secondly the human coronavirus OC43. Others are also important as SARS-CoV. In late 2019 the outbreak of Pneumonia occurred in the Chinese city of Wuhan which was investigated as a result of the corona virus, renamed as 2019-nCoV by the World Health Organization (WHO) and. now called as SARS-CoV-2. The WHO has identified the global health problem as an epidemic. Respiratory droplets produced during coughing and sneezing are the main means of transmission of COVID-19. Infection with COVID-19 in an infected person may remain undetected. Common symptoms of fever and dry cough are less common in the production of sputum, fatigue and in some cases may be dyspnoea or shortness of breath. The COVID-19 virus is a type of RNA virus, the outer envelope containing a lipid bilayer in which various proteins are synthesized such as membrane (M), envelope (E) and spike (S). Hand washing, coughing, social isolation, wearing a face mask in public, disinfection areas, and isolation are various ways to prevent the disease. The diagnosis of COVID-19 can be made on the basis of symptoms and confirmed using reverse transcription polymerase chain reaction (RT-PCR) tests. There are currently no antiretroviral drugs approved for COVID-19, only symptomatic and supportive treatment is used to treat people with this viral infection. Drugs that have been approved for the purpose of treating other viral infections are under investigation. Vaccination is an ultimate prevention and protection;few vaccines are given emergency approval and some are in progressive development phase in various countries to prevent this deadly pandemic. Copyright © 2022, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Sars-Cov-2 Novel Corona Virus: Origin and the Vaccination Survey

This paper manages the Origin of Covid (SARS-CoV-2-novel Covid) and the Vaccination view. Within excess of 10 million tainted cases and more than 3 million setbacks at the hour of composing this piece, the original Covid actuated wellbeing disease has arisen as the most serious among every one of the worldwide pandemics. The novel (COVID-19 or 2019-nCoV) was found in Wuhan, Hubei Province, China. Bats were liable for the underlying spread, which was subsequently spread to people by the raccoon canine and palm civet. The normal COVID-19 manifestations are fever, dry hack, and sleepiness. The significant manifestations are trouble breathing, chest torment, and loss of speech. The indications and indications of SARS-CoV-2 prompting COVID-19 completely match those of the occasional or, dust sensitivities and flu as migraine, touchiness of the throat, dry hack, weariness, fever, and at times loss of sensation (Tu et al., year2020). An individual tainted with the diseases of sensitivity to pollen or, flu sensitivity is additionally liable to show temperature that can be recorded with thermo-scanners prompting the individual to turn into a suspect of the sickness. Along these lines, before immunizing, a fast and exact analytic meter or, the pack is the need of great importance to identify the SARS-CoV-2 inferable from the way that the testing in view of PCR is tedious and exorbitant (Sirkeci and Yucesahin, year2020). Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

The Role of Social and Cultural Values in Pandemic Control in a Chinese Community: An Ethnographic Study on the Construction and Stigmatization of "Others" in Severe Acute Respiratory Syndrome (SARS) and COVID-19 in Hong Kong.

BACKGROUND: Studies have widely reported that social and cultural values serve as constraints in controlling the spread of an epidemic. However, I argue that a social and cultural value system is a double-edged sword and can motivate people's preventive health behaviors. Few studies have examined the positive role of social and cultural values in promoting epidemic control. METHODS: Using the severe acute respiratory syndrome outbreak in 2003 and the COVID-19 pandemic that began in 2020 in Hong Kong as examples, the present study performed participant observation in Hong Kong from January to June 2003 and from January 2020 to May 2022; in-depth individual semi-structured interviews were conducted with 70 participants between February 2021 and March 2022. RESULTS: Social and cultural values serve as informal social control mechanisms in manipulating people's adoption of preventive health behaviors that can assist in epidemic control. Specifically, the construction and stigmatization of the "others" groups and the traditional cultural values based on the capitalist ideology were noted to facilitate control measures against the two outbreaks in Hong Kong. CONCLUSION: These two outbreaks reinforced the embedded social and cultural values of the capitalist ideology of Hong Kong, which increased the vulnerability of disadvantaged social groups to stigmatization.

Atherosclerosis by Virus Infection-A Short Review.

Atherosclerosis manifests by the thickening of artery walls and their narrowed channels through the accumulation of plaque. It is one of the most important indicators of cardiovascular disease. It can be caused by various factors, such as smoking, a high cholesterol diet, hypertension, hyperglycemia, and genetic factors. However, atherosclerosis can also develop due to infection. It has been reported that some bacteria and viruses can cause the development of atherosclerosis. Examples of these viruses are influenza viruses, herpes viruses, hepatitis viruses, or papillomaviruses, which are all prevalent and eminent globally for infecting the population worldwide. Moreover, many patients with coronavirus disease 2019 (COVID-19) showed symptoms of cardiovascular disease. In this review paper, the viruses linked to the development of atherosclerosis are introduced, and their viral characteristics, the mechanisms of the development of atherosclerosis, and the current vaccines and antiviral treatment methods are summarized.

EPIDEMIOLOGIC ASPECTS IN PREVENTION OF THE NEW CORONAVIRUS INFECTION (COVID-19) (LITERATURE REVIEW)

At the end of 2019 the mankind had to face a new coronavirus infection with higher virulence which resulted in its rapid spread all over the world and in an ultimate pandemic. Initially a new virus which causes COVID-19 was called 2019-nCoV but it soon acquired its well-known name, SARS-CoV-2. We can positively state that this new coronavirus infection will remain in the history of world public healthcare as a disease that caused a collapse in rendering medical aid. Undoubtedly, this new coronavirus infection has changed customary lifestyle of the overall world population. This review can be considered problematic in its essence and focuses on examining contemporary trends in the official epidemiologic situation in the world regarding the new coronavirus infection (SARS-CoV-2). Having analyzed several foreign and domestic documents, the authors revealed a necessity to enhance levels and quality of COVID-19 epidemiologic diagnostics. There is a suggestion being considered at the moment on including additional clinical and diagnostic activities aimed at preventing further spread of the new coronavirus infection. We should note that data on COVID-19-related mortality and morbidity are renewed every day and every hour. Given that, it seems rather difficult to keep in line with the latest trends in COVID-19 prevention and epidemiologic diagnostics. However, the authors made an attempt to possibly collect all the latest data on epidemiological peculiarities related to the clinical course of the new coronavirus infection. The authors have a hope that this review will be useful for epidemiologists when they detect new cases of the disease as well as for lecturers at medical higher educational establishments when they train students and resident physicians. © Butaev T.M., Tsirikhova A.S., Kabaloeva D.V., Kudukhova D.O., 2022

Fatal SARS in X-Linked Lymphoproliferative Disease Type 1: A Case Report.

X-linked lymphoproliferative disease (XLP1) is an inborn error of immunity (IEI) with severe immune dysregulation caused by a mutation in the SH2D1A gene resulting in the absence or dysfunction of signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). The severe acute respiratory syndrome (SARS) caused by SARS-coronavirus (CoV), a highly pathogenic CoV, has been shown to only cause mild diseases in Asian children. We report on a 5-year-old Nepalese boy with agammaglobulinemia and probable SARS who died of diffuse alveolar damage 22 days after admission amid the SARS outbreak. The index patient and his younger brother were genetically confirmed to have XLP1. In the current coronavirus disease 2019 (COVID-19) pandemic, most children also had mild disease only. Children with severe COVID-19 would warrant investigations for underlying IEI, particularly along the pathways leading to immune dysregulation.

Angiotensin converting enzyme

Angiotensin converting enzyme (ACE) is well known for its dual actions to convert inactive Ang I to active Ang II, and degrades active bradykinin (BK), which plays an important role in controlling blood pressure. Because it is the bottleneck step for the production of pressor Ang II, it was targeted pharmacologically in the 1970s. Successful ACE inhibitors such as captopril were produced to treat hypertension. Studies on domain-specific ACE inhibitors are continuing to produce effective hypertension-controlling drugs with fewer side effects. ACE2 was discovered in 2000 and it converts Ang II into Ang(1-7), thereby reducing the concentration of Ang II as well as increasing that of Ang(1-7), an important enzyme for Ang(1-7)/Mas receptor signaling. ACE2 also acts as the receptor in the lung for the coronavirus, causing the infamous severe acute respiratory syndrome (SARS) in 2003. © 2021 Elsevier Inc. All rights reserved.

Out of the shadows: Impact of SARS experience on Chinese netizens' willingness to donate for COVID-19 pandemic prevention and control.

While charitable donations help to raise funds and contribute to pandemic prevention and control, there are many unanswered questions about how people make such donation decisions, especially in countries like China where charitable donations have played an increasing role in recent years. This study contributes to the literature by assessing the potential impacts of Chinese netizens' experience with the 2002 severe acute respiratory syndrome (SARS) epidemic on their willingness to donate for COVID-19 pandemic prevention and control. Specifically, this study applies a difference-in-differences (DID) model to a dataset collected from a nationwide survey to examine how individuals' exposure to the SARS epidemic affects their willingness to donate to alleviate the COVID-19 pandemic. The results suggest that individuals' SARS epidemic experiences in their early lives, especially during the "childhood-adolescence" period, had a lasting and far-reaching impact on their willingness to donate toward COVID-19 pandemic prevention and control. Also, the impacts were likely heterogeneous by such sociodemographic factors as educational background, health status, and income level. The empirical findings highlight the importance of considering early-life experiences in developing and implementing epidemic prevention and control policies. While the SARS experience likely affected Chinese netizens' willingness to donate toward COVID-19 pandemic prevention and control, lessons learned from both the SARS epidemic and COVID-19 pandemic could be used to develop more effective public health education and prevention programs as well as to increase public donations for future pandemic prevention and control.

Interplay of Influenza A/B Subtypes and COVID-19

Influenza, or most commonly termed the flu, is a common respiratory illness caused by viral infection. The circulation of this virus is found year-round but is more common during the flu season: fall and winter. In the United States, the number of reported cases begins to rise in October, reaches a peak in December, and returns to normal in April. Even though there are four subtypes of the Influenza virus, the seasonal flu outbreaks in humans are caused by type A and B viruses. eVision utilizes influenza data provided by the United States Center for Disease Control and Prevention (CDC) and the World Health Organization (WHO) to analyze influenza A and B cases throughout the flu season. During the 2019-20 flu season, the positive influenza cases reported in the US were between 36 and 56 million, which is the highest over the past six years. However, during the 2020-21 flu season which is the first complete flu season within the COVID-19 pandemic, the reported flu cases reduced drastically to 1,899;of which 713 were caused by influenza A viruses, and 1,186 by influenza B viruses. This indicates that the number of flu B cases was higher than that of flu A which was not normally the case prior to the COVID-19 pandemic. It was further observed that flu B reached its peak either at the same time or earlier than flu A which is also unusual compared to the flu trends prior to the onset of the COVID-19 pandemic. This peculiar trend is also noted during the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003. This paper reports the findings on deviation in the Influenza type A and type B trends during the circulation of Coronavirus in the US and Canada and provides possible reasons for these changes. © 2021 IEEE.

Investigation of the impact of SARS-CoV infection on the immunologic status and lung function after 15 years.

BACKGROUND: We investigate the long-term effects of SARS-CoV on patients' lung and immune systems 15 years post-infection. SARS-CoV-2 pandemic is ongoing however, another genetically related beta-coronavirus SARS-CoV caused an epidemic in 2003-2004. METHODS: We enrolled 58 healthcare workers from Peking University People's Hospital who were infected with SARS-CoV in 2003. We evaluated lung damage by mMRC score, pulmonary function tests, and chest CT. Immune function was assessed by their serum levels of globin, complete components, and peripheral T cell subsets. ELISA was used to detect SARS-CoV-specific IgG antibodies in sera. RESULTS: After 15 years of disease onset, 19 (36.5%), 8 (34.6%), and 19 (36.5%) subjects had impaired DL (CO), RV, and FEF25-75, respectively. 17 (30.4%) subjects had an mMRC score ≥ 2. Fourteen (25.5%) cases had residual CT abnormalities. T regulatory cells were a bit higher in the SARS survivors. IgG antibodies against SARS S-RBD protein and N protein were detected in 11 (18.97%) and 12 (20.69%) subjects, respectively. Subgroup analysis revealed that small airway dysfunction and CT abnormalities were more common in the severe group than in the non-severe group (57.1% vs 22.6%, 54.5% vs 6.1%, respectively, p < 0.05). CONCLUSIONS: SARS-CoV could cause permanent damage to the lung, which requires early pulmonary rehabilitation. The long-lived immune memory response against coronavirus requires further studies to assess the potential benefit. Trial registration ClinicalTrials.gov, NCT03443102. Registered prospectively on 25 January 2018.

Discovery of Highly Potent Fusion Inhibitors with Potential Pan-Coronavirus Activity That Effectively Inhibit Major COVID-19 Variants of Concern (VOCs) in Pseudovirus-Based Assays.

We report the discovery of several highly potent small molecules with low-nM potency against severe acute respiratory syndrome coronavirus (SARS-CoV; lowest half-maximal inhibitory concentration (IC50: 13 nM), SARS-CoV-2 (IC50: 23 nM), and Middle East respiratory syndrome coronavirus (MERS-CoV; IC50: 76 nM) in pseudovirus-based assays with excellent selectivity index (SI) values (>5000), demonstrating potential pan-coronavirus inhibitory activities. Some compounds showed 100% inhibition against the cytopathic effects (CPE; IC100) of an authentic SARS-CoV-2 (US_WA-1/2020) variant at 1.25 µM. The most active inhibitors also potently inhibited variants of concern (VOCs), including the UK (B.1.1.7) and South African (B.1.351) variants and the Delta variant (B.1.617.2) originally identified in India in pseudovirus-based assay. Surface plasmon resonance (SPR) analysis with one potent inhibitor confirmed that it binds to the prefusion SARS-CoV-2 spike protein trimer. These small-molecule inhibitors prevented virus-mediated cell-cell fusion. The absorption, distribution, metabolism, and excretion (ADME) data for one of the most active inhibitors, NBCoV1, demonstrated drug-like properties. An in vivo pharmacokinetics (PK) study of NBCoV1 in rats demonstrated an excellent half-life (t1/2) of 11.3 h, a mean resident time (MRT) of 14.2 h, and oral bioavailability. We expect these lead inhibitors to facilitate the further development of preclinical and clinical candidates.