Roles and functions of SARS-CoV-2 proteins in host immune evasion.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the host immune system through a variety of regulatory mechanisms. The genome of SARS-CoV-2 encodes 16 non-structural proteins (NSPs), four structural proteins, and nine accessory proteins that play indispensable roles to suppress the production and signaling of type I and III interferons (IFNs). In this review, we discussed the functions and the underlying mechanisms of different proteins of SARS-CoV-2 that evade the host immune system by suppressing the IFN-ß production and TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)/signal transducer and activator of transcription (STAT)1 and STAT2 phosphorylation. We also described different viral proteins inhibiting the nuclear translocation of IRF3, nuclear factor-κB (NF-κB), and STATs. To date, the following proteins of SARS-CoV-2 including NSP1, NSP6, NSP8, NSP12, NSP13, NSP14, NSP15, open reading frame (ORF)3a, ORF6, ORF8, ORF9b, ORF10, and Membrane (M) protein have been well studied. However, the detailed mechanisms of immune evasion by NSP5, ORF3b, ORF9c, and Nucleocapsid (N) proteins are not well elucidated. Additionally, we also elaborated the perspectives of SARS-CoV-2 proteins.

Roles and functions of SARS-CoV-2 proteins in host immune evasion

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the host immune system through a variety of regulatory mechanisms. The genome of SARS-CoV-2 encodes 16 non-structural proteins (NSPs), four structural proteins, and nine accessory proteins that play indispensable roles to suppress the production and signaling of type I and III interferons (IFNs). In this review, we discussed the functions and the underlying mechanisms of different proteins of SARS-CoV-2 that evade the host immune system by suppressing the IFN-β production and TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)/signal transducer and activator of transcription (STAT)1 and STAT2 phosphorylation. We also described different viral proteins inhibiting the nuclear translocation of IRF3, nuclear factor-κB (NF-κB), and STATs. To date, the following proteins of SARS-CoV-2 including NSP1, NSP6, NSP8, NSP12, NSP13, NSP14, NSP15, open reading frame (ORF)3a, ORF6, ORF8, ORF9b, ORF10, and Membrane (M) protein have been well studied. However, the detailed mechanisms of immune evasion by NSP5, ORF3b, ORF9c, and Nucleocapsid (N) proteins are not well elucidated. Additionally, we also elaborated the perspectives of SARS-CoV-2 proteins.

Neurological complications of COVID-19 in children and the associated immunological responses.

The high spread rate, severe symptoms, psychological and neurological problems, and unavailability of effective medicines are the major factors making Coronavirus disease 2019 (COVID-19) a massive threat to the world. It is thought that COVID-19 causes mild symptoms or mild infectious illness in children. However, we cannot rule out the possibility of serious complications such as the multisystem inflammatory syndrome. COVID-19 induces mild to severe neurological problems in children, such as stroke, encephalopathy, mild shortness of breath, and myalgia. The development of these conditions is associated with pro-inflammatory responses and cytokine storms, which alter the physiology of the blood-brain barrier and allow the virus to enter the brain. Despite the viral entry into the brain, these neurological conditions can also be caused indirectly by severe immune responses. In this article, we describe COVID-19 and the associated neurological and immunological complications in children.

The COVID-19 infection in children and its association with the immune system, prenatal stress, and neurological complications.

The Coronavirus disease 2019 (COVID-19)" caused by the "severe acute respiratory syndrome corona virus 2 (SARS-CoV-2)" has caused huge losses to the world due to the unavailability of effective treatment options. It is now a serious threat to humans as it causes severe respiratory disease, neurological complications, and other associated problems. Although COVID-19 generally causes mild and recoverable symptoms in children, it can cause serious severe symptoms and death causing complications. Most importantly, SARS-CoV-2 can cause neurological complications in children, such as shortness of breath, myalgia, stroke, and encephalopathy. These problems are highly linked with cytokine storm and proinflammatory responses, which can alter the physiology of the blood-brain barrier and allow the virus to enter the brain. Despite the direct infection caused by the virus entry into the brain, these neurological complications can result from indirect means such as severe immune responses. This review discusses viral transmission, transport to the brain, the associated prenatal stress, and neurological and/or immunological complications in children.

Exploring the interaction of quercetin-3-O-sophoroside with SARS-CoV-2 main proteins by theoretical studies: A probable prelude to control some variants of coronavirus including Delta.

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2's proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.

COVID-19 MANAGEMENT: TRADITIONAL CHINESE MEDICINE VS. WESTERN MEDICINAL ANTIVIRAL DRUGS, A REVIEW AND META-ANALYSIS

SARS-CoV-2 causing COVID-19 spread to more than 200 countries with 109 M infected patients and 2.41 M deaths (6.98% mortality rate). Currently, there is no approved drug or vaccine available to treat COVID-19 patients, though some combinations of already used broad-spectrum Western medicines, such as antibiotics, antivirals, and interferons are exploited against SARS-CoV-2. Among the Western medicines used, Chloroquine, Hydroxychloroquine, Chloroquine Phosphate, Remdesivir, and Umifenovir (Arbidol) were the most effective antivirals against SARS-CoV-2 at high or frequent dose. These drugs limited the viral infection by inhibiting attachment of virus to ACE2 receptor of human cell or by interfering and terminating the viral genome replication, but also induced severe adverse effects on the patients. Due to high and frequent dose of antivirals, patients reported with Hepatic, renal, and cardiac complications along with vomiting, diarrhea, muscle cramps, skin complications, anemia, abdominal pain, bleeding from nose, nausea, swelling of legs and ankles, hearing, and mental complications. Different vaccines are in trail phases might take long time to be available for COVID-19 patients, so an alternate therapy is required with no or minimal adverse effects. Chinese health workers significantly recovered the COVID-19 patients (92.4% recovery rate) by using their Traditional Chinese Medicine (TCM). The current review article contains details about the adverse effects of certain Western medicines, like antivirals on the COVID-19 patients and the efficacy of therapeutic herbal Traditional Chinese Medicine (TCM) for clinical recovery of CO VID-19 patients in China.

Vertical transmission potential of SARS-CoV-2 from infected mother to twin neonates.

Background: Limited details are available regarding the vertical transmission potential of COVID-19 infection in pregnant women. The authors' current study aimed to report the vertical transmission potential of COVID-19 infection in a woman pregnant with twins. Case description: The authors report the case of a 27-year-old woman infected with SARS-CoV-2. The patient was pregnant with dichorionic diamniotic fraternal twins and admitted to Renmin Hospital of Wuhan University, Wuhan, China. After undergoing a cesarean section, the patient gave birth to premature twins, who tested positive for COVID-19 infection. Interpretation: Findings from this case suggest a possibility of intrauterine infection caused by vertical transmission in a woman infected with COVID-19.

A review on the interaction of nucleoside analogues with SARS-CoV-2 RNA dependent RNA polymerase.

The outbreaks of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in 2019, have highlighted the concerns about the lack of potential vaccines or antivirals approved for inhibition of CoVs infection. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) which is almost preserved across different viral species can be a potential target for development of antiviral drugs, including nucleoside analogues (NA). However, ExoN proofreading activity of CoVs leads to their protection from several NAs. Therefore, potential platforms based on the development of efficient NAs with broad-spectrum efficacy against human CoVs should be explored. This study was then aimed to present an overview on the development of NAs-based drug repurposing for targeting SARS-CoV-2 RdRp by computational analysis. Afterwards, the clinical development of some NAs including Favipiravir, Sofosbuvir, Ribavirin, Tenofovir, and Remdesivir as potential inhibitors of RdRp, were surveyed. Overall, exploring broad-spectrum NAs as promising inhibitors of RdRp may provide useful information about the identification of potential antiviral repurposed drugs against SARS-CoV-2.

Coronaviruses disease 2019 (COVID-19): Causative agent, mental health concerns, and potential management options.

Coronavirus disease-2019 (COVID-19) pandemic started from Wuhan, China has infected more than 6.7 million individuals and killed more than 390,000 individuals globally. Due to the higher transmissibility and infectiousness, asymptomatic infection, and lack of effective treatment options and vaccine, fatalities and morbidities are increasing day by day globally. Despite physical health consequences, COVID-19 pandemic has created stress and anxiety, as result there is an increased risk of mental illnesses both in the infected and normal individuals. To eradicate these risks, it is necessary to determine the COVID-19 zoonotic source of transmission to humans and clinical manifestations in infected individuals. Although, identification or development of the highly effective therapeutic agents is necessary, however, development of protective strategies against the COVID-19 by enhancing immune responses will be an asset in the current scenarios of the COVID-19 pandemic. In this paper, we discuss the transmission, health consequences, and potential management (therapeutic and preventive) options for COVID-19 disease.

Rapid diagnostics of coronavirus disease 2019 in early stages using nanobiosensors: Challenges and opportunities.

The rapid outbreak of coronavirus disease 2019 (COVID-19) around the world is a tragic and shocking event that demonstrates the unpreparedness of humans to develop quick diagnostic platforms for novel infectious diseases. In fact, statistical reports of diagnostic tools show that their accuracy, specificity and sensitivity in the detection of COVID hampered by some challenges that can be eliminated by using nanoparticles (NPs). In this study, we aimed to present an overview on the most important ways to diagnose different kinds of viruses followed by the introduction of nanobiosensors. Afterward, some methods of COVID-19 detection such as imaging, laboratory and kit-based diagnostic tests are surveyed. Furthermore, nucleic acids/protein- and immunoglobulin (Ig)-based nanobiosensors for the COVID-19 detection infection are reviewed. Finally, current challenges and future perspective for the development of diagnostic or monitoring technologies in the control of COVID-19 are discussed to persuade the scientists in advancing their technologies beyond imagination. In conclusion, it can be deduced that as rapid COVID-19 detection infection can play a vital role in disease control and treatment, this review may be of great help for controlling the COVID-19 outbreak by providing some necessary information for the development of portable, accurate, selectable and simple nanobiosensors.

Coronavirus diseases 2019: Current biological situation and potential therapeutic perspective.

Coronavirus Disease 2019 (COVID-19) caused by a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first reported in Wuhan, China at the end of December 2019. SARS-CoV-2 is a highly pathogenic zoonotic virus and closely related to the Severe Acute Respiratory Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The COVID-19 was declared as a global pandemic due to its high infectiousness, and worldwide morbidities and mortalities. The Chinese scientists at the start of the outbreak reported genome sequences, which made the characterization of glycoproteins and other structural proteins possible. Moreover, researchers across the world have widely focused on understanding basic biology, developing vaccines, and therapeutic drugs against the COVID-19. However, until now, no promising treatment options, as well as vaccines, are available. In this review, we have described SARS-CoV-2's genome, transmission, and pathogenicity. We also discussed novel potential therapeutic agents that can help to treat the COVID-19 patients.

Mental health consequences of infections by coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

BACKGROUND: Anxiety and stress like mental illnesses are the common outcomes of viral epidemics and pandemics. Novel coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) was first reported in Wuhan, China, and then spread all over the world in a short time. OBJECTIVES: To highlight and discuss the impact of COVID-19 pandemic on mental or psychological health. METHOD: Literature search and collection of the information were performed using PubMed, the reports from the World health organization, and the Center for disease control and prevention. RESULTS: COVID-19 infection has already been declared as a global pandemic, which in association with infodemic has increased the risk of psychiatric/psychological disorders. A large population of the world is prone to develop anxiety, depressive disorders, and other mental abnormalities. Therefore, timely psychological interventions and preventive strategies are required. Moreover, the infection has been reported to be linked with cerebrovascular conditions; therefore, patients with underlying cerebrovascular diseases should be given attention. CONCLUSION: COVID-19-mediated mental health complications and cerebrovascular conditions may cause a huge burden on healthcare communities in the future. Therefore, timely intervention and the development or application of preventive strategies are required to decrease the risk of neurological consequences.

Evidence and speculations: vaccines and therapeutic options for COVID-19 pandemic.

A novel coronavirus (2019-nCov) emerged in China, at the end of December 2019 which posed an International Public Health Emergency, and later declared as a global pandemic by the World Health Organization (WHO). The International Committee on Taxonomy of Viruses (ICTV) named it SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), while the disease was named COVID-19 (Coronavirus Disease- 2019). Many questions related to the exact mode of transmission, animal origins, and antiviral therapeutics are not clear yet. Nevertheless, it is required to urgently launch a new protocol to evaluate the side effects of unapproved vaccines and antiviral therapeutics to accelerate the clinical application of new drugs. In this review, we highlight the most salient characteristics and recent findings of COVID-19 disease, molecular virology, interspecies mechanisms, and health consequences related to this disease.

COVID-19 around the world and the Chinese strategy to cope with SARS-CoV-2

SARS-CoV-2, a zoonotic virus, emerged in China causes Coronavirus Disease-2019 (COVID-19). Senior citizens and people with co-infections, genetic diseases, immune-compromised states, and cardiovascular diseases are at higher risk. There is no approved vaccine or drug available to treat COVID-19, although a few antivirals, interferon, and other drugs have reduced viral load in infected patients. However, these drugs have not been significantly effective in European countries. More than 40 different strains of SARS-CoV-2 have been detected in various parts of the world;they might have adapted themselves to the environmental conditions and have become resistant to therapeutic strategies. Many developed and developing countries are facing shortages of surgical masks and other protection tools. So far, the strategies developed by Chinese authorities have efficiently mitigated the SARS-CoV-2 transmission and limited mortality rate to less than 4%, with more than 78,000 people recovered from COVID-19. This review article highlights the pandemic conditions in different parts of the world, as well as possible reasons behind minimal COVID-19 infections and the high mortality rates. It will discuss information about China's strategies to cope with SARS-CoV-2 which can help other countries to mitigate viral spread and infection.