The influence of SARS-CoV-2 on male reproduction and men's health.

BACKGROUND: SARS-CoV-2, the virus responsible for COVID-19, primarily affects the respiratory system by targeting the Angiotensin-converting enzyme 2 (ACE2) receptor and TMPRSS2. However, these receptors are also present in other organs, including the testes, where a higher concentration of ACE2 receptors has been observed. This raises concerns about the potential impact of the virus on male fertility. AIMS: In this study, we aimed to assess the effects of SARS-CoV-2 on semen parameters by comparing samples during and after infection in the same patients. MATERIALS & METHOD: The study enrolled 51 individuals who had contracted COVID-19 and analysed various parameters related to sperm quality and quantity, including C-reactive protein, testosterone levels, total sperm concentration, motility and morphology. A comparison was made between these parameters during the initial infection with SARS-CoV-2 and after a 2- and 5-month recovery period. RESULTS: The results indicated that all of the mentioned parameters were significantly affected during COVID-19 infection (PCR-ct, CRP, WBCs LH, FSH and testosterone levels, p-value = .0001). Furthermore, the study assessed TC, TM and sperm morphology in patients infected with SARS-CoV-2 and found that these parameters were also significantly influenced during the infection, (p-value = .0001; Morphology, p-value = .0004). We observed significant alterations in sperm count and morphology during infection, suggesting a potential negative impact on sperm quality. Additionally, lower hormone levels were observed during COVID-19 infection, possibly due to increased inflammatory cytokines. However, both hormones and inflammation markers returned to normal following recovery. Our findings indicate a statistically significant change in total sperm count, motility and morphology post-infection, which aligns with previous studies. Discussion, COVID-19 have a transient impact on sperm parameters and fertility, emphasizing the importance of further investigation into the long-term implications.

Characterization of Entry Pathways, Species-Specific Angiotensin-Converting Enzyme 2 Residues Determining Entry, and Antibody Neutralization Evasion of Omicron BA.1, BA.1.1, BA.2, and BA.3 Variants.

The SARS-CoV-2 Omicron variants were first detected in November 2021, and several Omicron lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) have since rapidly emerged. Studies characterizing the mechanisms of Omicron variant infection and sensitivity to neutralizing antibodies induced upon vaccination are ongoing by several groups. In the present study, we used pseudoviruses to show that the transmembrane serine protease 2 (TMPRSS2) enhances infection of BA.1, BA.1.1, BA.2, and BA.3 Omicron variants to a lesser extent than ancestral D614G. We further show that Omicron variants have higher sensitivity to inhibition by soluble angiotensin-converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G. The Omicron variants also more efficiently used ACE2 receptors from 9 out of 10 animal species tested, and unlike the D614G variant, used mouse ACE2 due to the Q493R and Q498R spike substitutions. Finally, neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7- to 8-fold less potent than the D614G. These results provide insights into the transmissibility and immune evasion capacity of the emerging Omicron variants to curb their ongoing spread. IMPORTANCE The ongoing emergence of SARS-CoV-2 Omicron variants with an extensive number of spike mutations poses a significant public health and zoonotic concern due to enhanced transmission fitness and escape from neutralizing antibodies. We studied three Omicron lineage variants (BA.1, BA.2, and BA.3) and found that transmembrane serine protease 2 has less influence on Omicron entry into cells than on D614G, and Omicron exhibits greater sensitivity to endosomal entry inhibition compared to D614G. In addition, Omicron displays more efficient usage of diverse animal species ACE2 receptors than D614G. Furthermore, due to Q493R/Q498R substitutions in spike, Omicron, but not D614G, can use the mouse ACE2 receptor. Finally, three doses of Pfizer/BNT162b2 mRNA vaccination elicit high neutralization titers against Omicron variants, although the neutralization titers are still 7- to 8-fold lower those that against D614G. These results may give insights into the transmissibility and immune evasion capacity of the emerging Omicron variants to curb their ongoing spread.

SARS-CoV-2-mediated liver injury: pathophysiology and mechanisms of disease.

BACKGROUND: SARS-CoV-2-induced severe inflammatory response can be associated with severe medical consequences leading to multi-organ failure, including the liver. The main mechanism behind this assault is the aggressive cytokine storm that induces cytotoxicity in various organs. Of interest, hepatic stellate cells (HSC) respond acutely to liver injury through several molecular mechanisms, hence furthering the perpetuation of the cytokine storm and its resultant tissue damage. In addition, hepatocytes undergo apoptosis or necrosis resulting in the release of pro-inflammatory and pro-fibrogenic mediators that lead to chronic liver inflammation. AIMS: The aim of this review is to summarize available data on SARS-CoV-2-induced liver inflammation in addition to evaluate the potential effect of anti-inflammatory drugs in attenuating SARS-CoV-2-induced liver inflammation. METHODS: Thorough PubMed search was done to gather and summarize published data on SARS-CoV-2-induced liver inflammation. Additionally, various anti-inflammatory potential treatments were also documented. RESULTS: Published data documented SARS-CoV-2 infection of liver tissues and is prominent in most liver cells. Also, histological analysis showed various features of tissues damage, e.g., hepatocellular necrosis, mitosis, cellular infiltration, and fatty degeneration in addition to microvesicular steatosis and inflammation. Finally, the efficacy of the different drugs used to treat SARS-CoV-2-induced liver injury, in particular the anti-inflammatory remedies, are likely to have some beneficial effect to treat liver injury in COVID-19. CONCLUSION: SARS-CoV-2-induced liver inflammation is a serious condition, and drugs with potent anti-inflammatory effect can play a major role in preventing irreversible liver damage in COVID-19.

Myocardial injury in a patient with severe coronavirus disease: A case report.

INTRODUCTION: Coronavirus disease (COVID-19) can lead to severe disease or death and is characterized by a wide range of mild to severe symptoms. In addition to the lungs, studies have reported the involvement of the stomach, intestine, and angiotensin-converting enzyme 2 receptors in the heart. CASE REPORT: We present a case of a patient with COVID-19 who died soon after developing multi-organ failure and myocardial injury due to COVID-19-associated pneumonia. A 71-year-old man who contracted COVID-19 was admitted to the hospital after presenting with fever for 7 days and developed dyspnea. Following treatment, his respiratory status worsened. Thus, he was transferred to our hospital for intensive care on day 11. Physical examination revealed fever, dyspnea, respiratory distress, and no chest pain. Invasive positive pressure ventilation was initiated for acute respiratory distress syndrome on day 14. On day 15, we observed renal, liver, and coagulation dysfunction, indicating multi-organ failure. Chest radiography did not show clear signs of an increased cardiothoracic ratio or pulmonary congestion. An electrocardiogram (ECG) showed signs of myocardial infarction, which was confirmed by elevated troponin I and creatine kinase levels. The patient's circulatory dynamics did not improve on medication, and he died on day 16. CONCLUSIONS: We report the case of a patient with severe COVID-19 who died from an exacerbation of myocardial injury. Clinicians should not only evaluate respiration but also assess the heart by performing a 12-lead ECG, echocardiogram, and myocardial injury marker examination. Together, these tools can help predict which patients will develop severe COVID-19.

SARS coronavirus 2: from genome to infectome.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the group of Betacoronaviruses. The SARS-CoV-2 is closely related to SARS-CoV-1 and probably originated either from bats or pangolins. SARS-CoV-2 is an etiological agent of COVID-19, causing mild to severe respiratory disease which escalates to acute respiratory distress syndrome (ARDS) or multi-organ failure. The virus was first reported from the animal market in Hunan, Hubei province of China in the month of December, 2019, and was rapidly transmitted from animal to human and human-to-human. The human-to-human transmission can occur directly or via droplets generated during coughing and sneezing. Globally, around 53.9 million cases of COVID-19 have been registered with 1.31 million confirmed deaths. The people > 60 years, persons suffering from comorbid conditions and immunocompromised individuals are more susceptible to COVID-19 infection. The virus primarily targets the upper and the lower respiratory tract and quickly disseminates to other organs. SARS-CoV-2 dysregulates immune signaling pathways which generate cytokine storm and leads to the acute respiratory distress syndrome and other multisystemic disorders.

Naringenin, a flavanone with antiviral and anti-inflammatory effects: A promising treatment strategy against COVID-19.

At the end of 2019, a novel flu-like coronavirus named COVID-19 (coronavirus disease 2019) was recognized by World Health Organization. No specific treatments exist for COVID-19 at this time. New evidence suggests that therapeutic options focusing on antiviral agents may alleviate COVID-19 symptoms as well as those that lead to the decrease in the inflammatory responses. Flavonoids, as phenolic compounds, have attracted considerable attention due to their various biological properties. In this review, the promising effects and possible mechanisms of action of naringenin, a citrus-derived flavonoid, against COVID-19 were discussed. We searched PubMed/Medline, Science direct, Scopus, and Google Scholar databases up to March 2020 using the definitive keywords. The evidence reviewed here indicates that naringenin might exert therapeutic effects against COVID-19 through the inhibition of COVID-19 main protease, 3-chymotrypsin-like protease (3CLpro), and reduction of angiotensin converting enzyme receptors activity. One of the other mechanisms by which naringenin might exert therapeutic effects against COVID-19 is, at least partly, by attenuating inflammatory responses. The antiviral activity of the flavanone naringenin against some viruses has also been reported. On the whole, the favorable effects of naringenin lead to a conclusion that naringenin may be a promising treatment strategy against COVID-19.

Quercetin may reduce the risk of developing the symptoms of COVID-19.

Objective: Recent evidence reported that some dietary compounds like quercetin and apigenin as the most well-known flavonoids with anti-inflammatory effects may inhibit SARS-CoV-2 main protease. The hypothesis of the promising effects and possible mechanisms of action of quercetin against COVID-19 were assessed in this article. Materials and Methods: Related papers on the inhibitory effects of quercetin against COVID-19 were collected using the following search strategy: "corona or coronavirus or COVID or COVID-19 or viral or virus" AND "nutrient or flavonoid or Quercetin". Results: The findings indicated that quercetin can be considered an effective agent against COVID-19 because of its SARS-CoV-2 main protease and RNA-dependent RNA polymerase inhibitory effects. In addition, quercetin may attenuate angiotensin-converting enzyme-2 (ACE-2) receptors leading to a reduction of SARS-CoV-2 ability to enter host cells. Moreover, the antiviral, anti-inflammatory, and immunomodulatory activities of quercetin have been frequently reported. Conclusion: Quercetin may be an effective agent for managing the complications of COVID-19. Further longitudinal human studies are warranted.

Patients with Hepatitis C Undergoing Direct-Acting Antiviral Treatment Have a Lower SARS-CoV-2 Infection Rate.

This study retrospectively analyzed the medical records of 602 patients with first-time positive results for the HCV nucleic acid test between 1 May 2021 and 31 March 2023, exploring the association between DAA treatment and SARS-CoV-2 infection. The results showed that 9.8% of HCV patients were co-infected with SARS-CoV-2. Gender, age, vaccination status, and HCV genotype did not significantly affect SARS-CoV-2 infection. However, patients undergoing DAA treatment showed significantly lower rates of SARS-CoV-2 infection and mortality compared to those not undergoing DAA treatment. The analysis also compared patients undergoing different DAA treatments, with Epclusa and Maviret showing superior protection against SARS-CoV-2. Furthermore, this study explored the severity and mortality of SARS-CoV-2 infection in patients undergoing and having completed DAA treatment. It revealed that patients diagnosed with COVID-19 during DAA treatment experienced only mild symptoms, and none died, suggesting a potential protective effect of DAA treatment against severe outcomes of SARS-CoV-2 infection. The findings contribute to the understanding of the interplay between HCV, DAA treatment, and SARS-CoV-2 infection, highlighting the need for continued monitoring and healthcare measures for individuals with chronic conditions during the ongoing COVID-19 pandemic.

[Systemic and extrapulmonary manifestations of COVID-19]. / Manifestaciones sistémicas y extrapulmonares en la COVID-19.

Although fever and respiratory symptoms are the main clinical expression of COVID-19 disease, important extrapulmonary complications that affect the majority of the organs and systems may occur. Multisystemic involvement can mainly be attributed to the generalized location of ACE2 receptors throughout the body, which act as the main point of entry for the virus. Systemic manifestations may occasionally appear before the typical symptoms, although they generally occur later or are sequelae of the disease. Thromboembolic complications are concerning due to their frequency and severity; they are the result of a hypercoagulable state with multiple possible clinical manifestations. Cardiac, neurological, gastrointestinal, renal, endocrine-metabolic, skin, and ocular complications may occur. The manifestations and specific therapeutic aspects of COVID-19 disease in pregnant women as well as implications of the disease on children are discussed. The corresponding tests must be performed in all patients with a clinical suspicion of COVID-19 in order to confirm the diagnosis of the infection. The specific diagnostic tests that are indicative of involvement of different organs are guided based on clinical suspicion. These tests are conducted on an individual basis taking into account the isolation measures required and the severity of each case. Likewise, the corresponding treatment is administered according to criteria that generally similar to those for the general population.

Covid 19-the 21st Century Pandemic: The Novel Coronavirus Outbreak and the Treatment Strategies.

COVID -19 a global pandemic that has brought all the greater global countries to a hook. The novel coronavirus (SARS-CoV-2) outbreak was first reported in Wuhan, China which then started spreading to different countries around the world. ACE2 receptors are present in various organs but the overexpression of ACE2 at lung epithelia makes them more vulnerable to respiratory symptoms. SARS-CoV-2 binds to ACE2 receptors for entry into host cells which may serve as potential target for future therapy.Repurposing of drugs are the present strategy undertaken as the SARS-CoV-2 shows similar respiratory distress symptoms as in the case of SARS and MERS. At present the antiviral medications and vaccines are at the early stages and may take few months to years, to achieve their complete efficacy to solve the public crisis. The technological advancements have brought passive immunisation, which is an anecdotal success, but the ideal approach to future outbreaks of SARS-CoV-2 is done by vaccines that are under clinical trials. There are a large percentage of population under psychological crisis either due to the fear of infection or stress from the quarantine lives. High levels of viral loads at the initial stages cause higher chances of transmission hence immediate isolations and screening methods must be undertaken. This review mainly focuses on the treatment strategies followed with no definitive approval from authorities. This is an attempt to gather all the materialistic evidences available for now.

Angiotensin-converting enzyme 2 as a potential therapeutic target for COVID-19: A review.

As of August 16, 2021, there have been 207,173,086 confirmed cases and 4,361,996 deaths due to the coronavirus disease (COVID-19), and the pandemic remains a global challenge. To date, no effective and approved drugs are available for the treatment of COVID-19. Angiotensin-converting enzyme 2 (ACE2) plays a crucial role in the invasion into host cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19. Notably, ACE2 density is influenced by medical conditions, such as hypertension, or by drugs, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which can change the fate of SARS-CoV-2 infectivity. ACE2 is a target for these drugs and can be manipulated to limit the viral entry and replication within the cells. Different strategies aimed at blocking ACE2 with small molecules, peptides, and antibodies, or by neutralizing the virus through its competitive binding with human recombinant soluble ACE2 (hrsACE2) are currently under investigation. In this article, we review the current state of knowledge that emphasizes the need to find effective therapeutic agents against COVID-19 by exploiting ACE2 as a potential target. The increased soluble ACE2 levels and the application of hrsACE2 in patients with COVID-19 can be implemented to control the disease. It has not yet been established whether hypertension and other comorbidities, independent of age, have a direct role in COVID-19. Therefore, the use of renin-angiotensin system inhibitors, ACEIs and ARBs, should not be discontinued during COVID-19 treatment.

Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy.

Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients' organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera, which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future.

Molecular dynamics simulations highlight the altered binding landscape at the spike-ACE2 interface between the Delta and Omicron variants compared to the SARS-CoV-2 original strain.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 variant (Omicron), represents a significant deviation in genetic makeup and function compared to previous variants. Following the BA.1 sublineage, the BA.2 and BA.3 Omicron subvariants became dominant, and currently the BA.4 and BA.5, which are quite distinct variants, have emerged. Using molecular dynamics simulations, we investigated the binding characteristics of the Delta and Omicron (BA.1) variants in comparison to wild-type (WT) at the interface of the spike protein receptor binding domain (RBD) and human angiotensin converting enzyme-2 (ACE2) ectodomain. The primary aim was to compare our molecular modelling systems with previously published observations, to determine the robustness of our approach for rapid prediction of emerging future variants. Delta and Omicron were found to bind to ACE2 with similar affinities (-39.4 and -43.3 kcal/mol, respectively) and stronger than WT (-33.5 kcal/mol). In line with previously published observations, the energy contributions of the non-mutated residues at the interface were largely retained between WT and the variants, with F456, F486, and Y489 having the strongest energy contributions to ACE2 binding. Further, residues N440K, Q498R, and N501Y were predicted to be energetically favourable in Omicron. In contrast to Omicron, which had the E484A and K417N mutations, intermolecular bonds were detected for the residue pairs E484:K31 and K417:D30 in WT and Delta, in accordance with previously published findings. Overall, our simplified molecular modelling approach represents a step towards predictive model systems for rapidly analysing arising variants of concern.

Comparative Analysis of Susceptibility and Severity of COVID-19 in Countries from the Eastern and the Western World Till March '21.

Majority of the world's human population today is affected by Covid-19. The disease has not only exhibited differences in susceptibility among people of different countries, but also the mortality rate. In general, Western world has been reporting a greater number of infected cases than eastern countries. Even the mortality rates are quite high there. The aim of this study was to analyse the data available on the infectivity and mortality rates of Covid-19 in different countries till March'21 and then reviewed the literature to find reasons for the differences in susceptibility and severity in eastern and western countries. The reasons for the observed differences may be: (i) Eastern countries followed stricter modalities and got grace period to create better healthcare facilities to tackle COVID-19. This probably also slowed the transmission of virus and its evolution, (ii) Vaccination policies in the east may have provided some immunity due to cross reactivity, (iii) Frequent exposure to infections at young age in eastern countries might be helping in better immunity, (iv) Mutations in viral genome may be geography based and (v) Genetic differences in the immune system of the hosts with respect to ACE receptors and MHC may be playing an important role. In this article, an attempt has been made to put forth and discuss these plausible reasons along with suitable evidences. These findings may help in future research on the diagnosis, treatment and prevention of Covid-19.

CRISPR Technology in Gene-Editing-Based Detection and Treatment of SARS-CoV-2.

Outbreak and rapid spread of coronavirus disease (COVID-19) caused by coronavirus acute respiratory syndrome (SARS-CoV-2) caused severe acute respiratory syndrome (SARS-CoV-2) that started in Wuhan, and has become a global problem because of the high rate of human-to-human transmission and severe respiratory infections. Because of high prevalence of SARS-CoV-2, which threatens many people worldwide, rapid diagnosis and simple treatment are needed. Genome editing is a nucleic acid-based approach to altering the genome by artificially changes in genetic information and induce irreversible changes in the function of target gene. Clustered, regularly interspaced short palindromic repeats (CRISPR/Cas) could be a practical and straightforward approach to this disease. CRISPR/Cas system contains Cas protein, which is controlled by a small RNA molecule to create a double-stranded DNA gap. Evidence suggested that CRISPR/Cas was also usable for diagnosis and treatment of SARS-CoV-2 infection. In this review study, we discoursed on application of CRISPR technology in detection and treatment of SARS-CoV-2 infection. Another aspect of this study was to introduce potential future problems in use of CRISPR/Cas technology.

[COVID-19 related stroke]. / Insul't, assotsiirovannyi s COVID-19.

The COVID-19 pandemic had a significant impact on both the incidence of acute cerebral circulatory disorders and the structure of mortality. SARS-CoV-2 increases the risk of both ischemic and hemorrhagic stroke. The key pathogenetic links underlying the development of cerebral stroke in COVID-19 are impaired functioning of angiotensin 2 receptors, accompanied by the accumulation of excess angiotensin 2, endothelial dysfunction, hypercoagulation, hyperproduction of proinflammatory cytokines and oxidative storm. In patients with stroke and COVID-19, the severity of the lesion is associated with a dual mechanism of ischemia - systemic and cerebral. The possibilities of medical correction of systemic disorders associated with coronavirus infection, as well as local ones caused by ischemic or hemorrhagic brain damage, are limited. Substances with antioxidant activity could potentially be effective in patients with stroke and COVID-1.

Cross Talk between COVID-19 and Breast Cancer.

Cancer patients are more susceptible to COVID-19; however, the prevalence of COVID-19 in different types of cancer is still inconsistent and inconclusive. Here, we delineate the intricate relationship between breast cancer and COVID-19. Breast cancer and COVID-19 share the involvement of common comorbidities, hormonal signalling pathways, gender differences, rennin- angiotensin system (RAS), angiotensin-converting enzyme-2 (ACE-2), transmembrane protease serine 2 (TMPRSS2) and dipeptidyl peptidase-IV (DPP-IV). We also shed light on the possible effects of therapeutic modalities of COVID-19 on breast cancer outcomes. Briefly, we conclude that breast cancer patients are more susceptible to COVID-19 in comparison with their normal counterparts. Women are more resistant to the occurrence and severity of COVID-19. Increased expressions of ACE2 and TMPRSS2 are correlated with occurrence and severity of COVID-19, but higher expression of ACE2 and lower expression of TMPRSS2 are prognostic markers for overall disease free survival in breast cancer. The ACE2 inhibitors and ibuprofen therapies for COVID-19 treatment may aggravate the clinical condition of breast cancer patients through chemo-resistance and metastasis. Most of the available therapeutic modalities for COVID-19 were also found to exert positive effects on breast cancer outcomes. Besides drugs in clinical trend, TMPRSS2 inhibitors, estrogen supplementation, androgen deprivation and DPP-IV inhibitors may also be used to treat breast cancer patients infected with SARS-CoV-2. However, drug-drug interactions suggest that some of the drugs used for the treatment of COVID-19 may modulate the drug metabolism of anticancer therapies which may lead to adverse drug reaction events.

The Ineluctable Role of ACE-2 Receptors in SARS COV-2 Infection and Drug Repurposing as a Plausible SARS COV-2 Therapy: A Concise Treatise.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the COVID-19 infectious disease that spreads via the respiratory route and has reached a drastic level of a global pandemic. Symptoms of COVID-19 may vary from mild (fever, dry cough, shortness of breath) to severe pneumonia-like respiratory symptoms as exacerbation of disease occurs. Unlike SARS-CoV, the SARSCoV- 2 has a higher binding affinity to ACE-2 receptors, which signifies its higher transmission rate from person to person. Even though ACE-2 is significant in the reninangiotensin- aldosterone system (RAAS) regulation that exhibits protection to various organs, it plays a significant role in COVID-19 disease pathogenesis. Viral interferences with the ACE-2 peptidase activity are found in SARS-CoV-2 infected patients leading to pro-inflammatory responses, hypertension and multi-organ damage. Angiotensinconverting enzyme-2 is constrained to a variety of organ systems, but surface ACE-2 receptors on lung epithelia are largely affected, which lead to pathological alterations in lung histology which may progress to respiratory failure. The viral tropism mainly occurs by the attachment to the angiotensin-converting enzymes-2 receptors in the host cell; thus drugs targeting ACE-2 expressions may arise as the future therapeutic strategy to combat COVID-19 infections. The innovative approach of repurposing drugs has shown temporary effectiveness to curb the rising pandemic. This article mainly focuses on the prominence of ACE-2 receptors which are expressed during the COVID infections and the repurposing strategy of available drug therapies.

COVID-19: a new emerging respiratory disease from the neurological perspective.

Coronavirus disease 2019 (COVID-19) has become a challenging public health catastrophe worldwide. The newly emerged disease spread in almost all countries and infected 100 million persons worldwide. The infection is not limited to the respiratory system but involves various body systems and may lead to multiple organ failure. Tissue degenerative changes result from direct viral invasion, indirect consequences, or through an uncontrolled immune response. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads to the brain via hematogenous and neural routes accompanied with dysfunction of the blood-brain barrier. The involvement of the central nervous system is now suspected to be among the main causes of death. The present review discusses the historical background of coronaviruses, their role in previous and ongoing pandemics, the way they escape the immune system, why they are able to spread despite all undertaken measures, in addition to the neurological manifestations, long-term consequences of the disease, and various routes of viral introduction to the CNS.

RNAi Technology and Investigation on Possible Vaccines to Combat SARS-CoV-2 Infection.

Coronavirus disease of 2019 (COVID-19) pandemic, taking place globally, occurs as a result of the SARS-CoV-2 viral infection which has caused death of innumerable numbers of people and is responsible for a massive drop in the global economy. Millions of people are infected, and the death rate is also quite high in different countries. So, there is an urgent requirement of the invention of some effective and efficient drugs that can be effective against this deadly viral infection. The invention of new drugs and vaccine has become a matter of utmost importance to stop the mayhem of coronavirus pandemic. In the middle of such a deadly pandemic, the necessity of development of a vaccine is of high importance in this context. Among all the popular methods of vaccine development, the mRNA vaccines turned out to be the one of the most versatile vaccine with quick responses. However, in this review, we have explained all the possible types of vaccines available including DNA vaccines, RNA vaccines, and live and attenuated vaccines. Their effectiveness, importance, and application of the vaccines against the SARS-CoV-2 virus have been discussed. Research is also being conducted in the field of gene silencing, and one of the best possible ways to combat the virus at the molecular level is by applying RNAi technology. The modified siRNA molecules can be used to silence the gene expression of the virus. A summarization of the virus's behavior, characteristics, and the methods by which RNAi technology can be administered to control the virus is depicted in this study.