SARS-CoV-2: An Update on Potential Antivirals in Light of SARS-CoV Antiviral Drug Discoveries

Coronaviruses (CoVs) are a group of RNA viruses that are associated with different diseases in animals, birds, and humans. Human CoVs (HCoVs) have long been known to be the causative agents of mild respiratory illnesses. However, two HCoVs associated with severe respiratory diseases are Severe Acute Respiratory Syndrome-CoV (SARS-CoV) and Middle East Respiratory Syndrome-CoV (MERS-CoV). Both viruses resulted in hundreds of deaths after spreading to several countries. Most recently, SARS-CoV-2 has emerged as the third HCoV causing severe respiratory distress syndrome and viral pneumonia (known as COVID-19) in patients from Wuhan, China, in December 2019. Soon after its discovery, SARS-CoV-2 spread to all countries, resulting in millions of cases and thousands of deaths. Since the emergence of SARS-CoV, many research groups have dedicated their resources to discovering effective antivirals that can treat such life-threatening infections. The rapid spread and high fatality rate of SARS-CoV-2 necessitate the quick discovery of effective antivirals to control this outbreak. Since SARS-CoV-2 shares 79% sequence identity with SARS-CoV, several anti-SARS-CoV drugs have shown promise in limiting SARS-CoV-2 replication in vitro and in vivo. In this review, we discuss antivirals described for SARS-CoV and provide an update on therapeutic strategies and antivirals against SARS-CoV-2. The control of the current outbreak will strongly depend on the discovery of effective and safe anti-SARS-CoV-2 drugs

Dermatological manifestations of tick-borne viral infections found in the United States

Abstract Tick-borne diseases (TBDs) are bacterial, viral, and parasitic diseases transmitted by ticks. Viral TBDs have increased in prevalence over the last decade with many new pathogenic viruses being discovered. Doxycycline is often empirically prescribed by clinicians to treat symptomatic patients following tick bites due to suspicions of bacterial TBDs such as Rocky Mountain spotted fever, anaplasmosis, and ehrlichiosis. However, viral TBDs are included in the differential diagnosis if patients do not clinically improve following antibiotic therapy. Several viral TBDs present with dermatological manifestations. Recognizing the differences in clinical presentations of TBDs, particularly of newly emerging viral TBDs in the United States, can help physicians identify the viral TBD, and possibly rule out viral illnesses with different clinical presentations. Therefore, this review discusses clinical manifestations, with an emphasis on dermatologic manifestations of Heartland Virus, Bourbon Virus, Powassan Virus, Deer Tick Virus and Colorado Tick Fever Virus. Key points Viral tick-borne diseases have increased in prevalence over the last decade and often have similar clinical manifestations to other tick-borne diseases, including bacterial infections. Here, we review the dermatologic manifestations of Heartland Virus (HRTV), Bourbon Virus (BRBV), Powassan Virus (POWV), Deer Tick Virus (DTV) and Colorado Tick Fever Virus (CTFV) that are important for clinicians

Insights into the recent 2019 novel coronavirus (Sars-coV-2) in light of past human coronavirus outbreaks

Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Human Monoclonal Antibodies against Highly Conserved HR1 and HR2 Domains of the SARS-CoV Spike Protein Are More Broadly Neutralizing

Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for generating therapeutic antibodies or subunit vaccines against other enveloped viruses

Assessment of Anxiety, Depression, Attitude, and Coping Strategies of the Egyptian Population during the COVID-19 Pandemic

Background: The COVID-19 pandemic has imposed several challenges on different populations all around the world, with stress being identified as one of the major challenges. This study aims to investigate the impact of COVID-19-induced stress on the prevalence and severity of anxiety and/or depression, factors that predict the development of anxiety and/or depression, and coping strategies in the Egyptian population during the COVID 19 outbreak. Subjects and Methods: This is an observational cross-sectional online study. The questionnaire of our study included five sections: demographic and clinical data, attitude towards COVID-19, the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory-II (BDI-II), and a specifically prepared and standardized Arabic version of a coping strategies scale. The questionnaire was uploaded on 20 May 2020 at 1 p.m. and closed on 7 July 2020 at 8 a.m. Results: The study questionnaire was completed by 283 Egyptians, with mean age 34.81 ± 11.36 years, of which 17% had been infected with COVID-19. The responses showed that 62.9% had moderate anxiety, whereas 12.4% had severe anxiety. Moreover, 13.8% had moderate depression, and 14.1% had severe depression. Our study demonstrated that age, mental status, and being infected with COVID-19 correlated with depression, whereas only age correlated with anxiety. Interestingly, our data showed that anxiety and depression were negatively correlated with some coping strategies during the COVID-19 pandemic. Conclusions: Pandemics, such as the COVID-19 pandemic, imposes stress on individuals, which leads to the development of anxiety and/or depression. Several factors, which could be population-dependent, may help predict the development of anxiety or depression. We show the factors correlated with depression and anxiety during the COVID-19 pandemic in the Egyptian population. Furthermore, certain personal coping strategies during the COVID-19 pandemic are negatively correlated with anxiety and depression. Therefore, our study sheds light on the importance of studying factors in each population that can lead to pandemic-induced psychological complications and those that can relieve such complications

Anticoronavirus and Immunomodulatory Phenolic Compounds: Opportunities and Pharmacotherapeutic Perspectives

In 2019, COVID-19 emerged as a severe respiratory disease that is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The disease has been associated with high mortality rate, especially in patients with comorbidities such as diabetes, cardiovascular and kidney diseases. This could be attributed to dysregulated immune responses and severe systemic inflammation in COVID-19 patients. The use of effective antiviral drugs against SARS-CoV-2 and modulation of the immune responses could be a potential therapeutic strategy for COVID-19. Studies have shown that natural phenolic compounds have several pharmacological properties, including anticoronavirus and immunomodulatory activities. Therefore, this review discusses the dual action of these natural products from the perspective of applicability at COVID-19

Reactivity of the18 Neutralizing HmAbs with SARS CoV 12-510-S1 proteins.

<p>Medisorp ELISA plates were coated with 100 ng/well of Urbani and RBD mutant 12-510S1-IgG proteins and 2.5 µg/ml of each HmAb was used as the primary antibody. Anti-human IgG2 HRP mouse monoclonal antibody was used as secondary antibody. OD was measured at 450 nm. Error bars represent SD of a representative experiment performed in triplicates. (A) Urbani versus Sin845 mutant. (B) Urbani versus GD01 mutant. (C) Urbani versus GZ0402 mutant. (D) Urbani versus GZ-C mutant.</p

<i>In vitro</i> pseudovirus neutralization assay.

<p>Eighteen neutralizing HmAbs were tested against different mutant as well as Urbani pseudoviruses. Pseudoviruses equivalent to 10 ng of HIVp24 were incubated for 1 hr with 25 µg/ml of each of the HmAbs at 37°C. The virus/Ab mixtures were then added to 293/ACE2 stable cell line. Seventy two hours later, the virus entry was determined by luciferase expression. The percentage entry inhibitions obtained with Abs were calculated and normalized to HIV/Urbani-S inhibitions (A) HIV/GZ-C and HIV/Sin845 inhibitions (B) HIV/GZ0402 and HIV/GD01 inhibitions. Polyclonal rabbit immune serum (PolyAb) was used as a positive control. Error bars represent SD of a representative experiment performed in triplicates.</p

Combinations of HmAbs more efficiently inhibit the entry of SARS-CoV RBD surrogate clinical isolates.

<p>Neutralizing HmAbs binding to different regions of S protein 4D4 (S1), 1F8 (HR1), 5E9 (HR2)) were tested for their ability to neutralize pseudoviruses in different combinations as well as individually at a concentration of 6.25 µg/ml each. The virus/Ab mixture was incubated for 1 hr at 37°C then added to 293/ACE2 stable cell line. Seventy two hours later, the virus entry was determined by luciferase expression. The percentage entry inhibitions by individual antibodies as well as combinations of antibodies were calculated. Error bars represent SD of representative experiment performed in triplicates. Statistical analysis was done using Student-t test, significant differences are indicated by asterisks,<i>* p<0.05.</i></p