Active Components of Commonly Prescribed Medicines Affect Influenza A Virus–Host Cell Interaction: A Pilot Study

Background: Every year, millions of people are hospitalized and thousands die from influenza A virus (FLUAV) infection. Most cases of hospitalizations and death occur among the elderly. Many of these elderly patients are reliant on medical treatment of underlying chronic diseases, such as arthritis, diabetes, and hypertension. We hypothesized that the commonly prescribed medicines for treatment of underlying chronic diseases can affect host responses to FLUAV infection and thus contribute to the morbidity and mortality associated with influenza. Therefore, the aim of this study was to examine whether commonly prescribed medicines could affect host responses to virus infection in vitro. Methods: We first identified 45 active compounds from a list of commonly prescribed medicines. Then, we constructed a drug–target interaction network and identified the potential implication of these interactions for FLUAV–host cell interplay. Finally, we tested the effect of 45 drugs on the viability, transcription, and metabolism of mock- and FLUAV-infected human retinal pigment epithelial (RPE) cells. Results: In silico drug–target interaction analysis revealed that drugs such as atorvastatin, candesartan, and hydroxocobalamin could target and modulate FLUAV–host cell interaction. In vitro experiments showed that at non-cytotoxic concentrations, these compounds affected the transcription and metabolism of FLUAV- and mock-infected cells. Conclusion: Many commonly prescribed drugs were found to modulate FLUAV–host cell interactions in silico and in vitro and could therefore affect their interplay in vivo, thus contributing to the morbidity and mortality of patients with influenza virus infections.

Severe Acute Respiratory Coronavirus-2: A Critical Review of Virus Biology, Genome and Pathophysiology

Severe Acute Respiratory Coronavirus-2 [SARS-CoV-2] emerged as a great threat to the world at the end of December 2019 in China. The SARS-CoV-2 evolved from a virus responsible for the SARS epidemic in 2002. The SARS-CoV-2 has a high rate of human-human transmission and originated from the bat. It has a close resemblance with bat-like-SARS-CoV compared to SARS-CoV; however, the Spike protein responsible for virus-host cell interaction possesses the least similarity with that of SARS-CoV. Cytokine Storm is associated with the severity of Covid-19 and leads to acute respiratory distress syndrome [ARDS] and/or multiple organ dysfunction syndromes [MODS]. In the current review article, the features of a novel coronavirus, including viral biology, genomic organisation, life cycle, pathophysiology and genetic diversity, have been discussed. The development of policies and plans which can prepare the world for future pandemics has also been proposed. In addition, the drug development pipelines, diagnostic facilities and management of such pandemics need an up-gradation to contain the current as well as future outbreaks.

Active Components of Commonly Prescribed Medicines Affect Influenza a Virus-Host Cell Interaction: A Pilot Study

Background: Every year, millions of people are hospitalized, and thousands die from influenza A virus (FLUAV) infection. Most cases of hospitalizations and death occur among elderly. Many of these elderly patients are reliant on medical treatment of underlying chronic diseases, such as arthritis, diabetes, and hypertension. We hypothesized that the commonly prescribed medicines for treatment of underlying chronic diseases can affect host responses to FLUAV infection, and thus contribute to morbidity and mortality associated with influenza. Therefore, the aim of this study was to examine whether commonly prescribed medicines could affect host responses to virus infection in vitro. Methods: We first identified 45 active compounds of medicines commonly prescribed in Central Norway. Then we constructed a drug-target interaction network and identified potential implication of these interactions for FLUAV-host cell interplay. Finally, we tested the effect of 45 drugs on viability, transcription and metabolism of mock- and A/WSN/33(H1N1)-infected human retinal pigment epithelial (RPE) cells. Results: In silico drug-target interaction analysis revealed that many drugs, such as acetylsalicylic acid, atorvastatin, candesartan, and hydroxocobalam, could target and modulate FLUAV-host cell interaction. In vitro experiments showed that these and other compounds at non-cytotoxic concentrations differently affected transcription and metabolism of mock- and FLUAV-infected cells. Conclusion: Many commonly prescribed drugs modulate FLUAV-host cell interactions in vitro and therefore could affect their interplay in vivo, thus, contributing to morbidity and mortality of patients with influenza virus infections.

Active components of commonly prescribed medicines affect influenza A virus-host cell interaction: a pilot study

Background: Every year, millions of people are hospitalized, and thousands die from influenza A virus (FLUAV) infection. Most cases of hospitalizations and death occur among elderly. Many of these elderly patients are reliant on medical treatment of underlying chronic diseases, such as arthritis, diabetes, and hypertension. We hypothesized that the commonly prescribed medicines for treatment of underlying chronic diseases can affect host responses to FLUAV infection, and thus contribute to morbidity and mortality associated with influenza. Therefore, the aim of this study was to examine whether commonly prescribed medicines could affect host responses to virus infection in vitro. Methods: We first identified 45 active compounds of commonly prescribed medicines. Then we constructed a drug-target interaction network and identified potential implication of these interactions for FLUAV-host cell interplay. Finally, we tested the effect of 45 drugs on viability, transcription and metabolism of mock- and FLUAV-infected human retinal pigment epithelial (RPE) cells. Results: In silico drug-target interaction analysis revealed that many drugs, such as atorvastatin, candesartan, and hydroxocobalam, could target and modulate FLUAV-host cell interaction. In vitro experiments showed that these and other compounds at non-cytotoxic concentrations differently affected transcription and metabolism of mock- and FLUAV-infected cells. Conclusion: Many commonly prescribed drugs modulate FLUAV-host cell interactions in silico and in vitro and, therefore, could affect their interplay in vivo, thus, contributing to morbidity and mortality of patients with influenza virus infections.

Why Does SARS-CoV-2 Infection Induce Autoantibody Production?

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient’s immune system may reflect (1) the dysregulation of the immune response or (2) it may be an attempt to regulate itself in situations where the non-infectious self poses a greater threat than the infectious non-self. Of significance may be the primary virus-host cell interaction where the surface-bound ACE2 ectoenzyme plays a critical role. Here, we present a brief analysis of recent findings concerning the immune recognition of SARS-CoV-2, which, we believe, favors the second possibility as the underlying reason for the production of autoantibodies during COVID-19.

Hazara virus and Crimean-Congo Hemorrhagic Fever Virus show a different pattern of entry in fully-polarized Caco-2 cell line

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) and Hazara virus (HAZV) belong to the same viral serotype and family. HAZV has lately been used as a model system and surrogate to CCHFV. However, virus-host cell interaction and level of pathogenicity for these viruses are not well investigated nor compared. In this study, we compared HAZV and CCHFV infection of human polarized epithelial cells to shed light on similarities and differences in virus-host cell interaction between these two viruses. We investigated the pattern of infection of CCHFV and HAZV in fully polarized human cells, the Caco-2 cell line. Polarization of Caco-2 cells lead to difference in expression level and pattern of proteins between the apical and the basolateral membranes. We found that CCHFV virus, in contrast to HAZV, is more likely infecting polarized cells basolaterally. In addition, we found that cytokines/pro-inflammatory factors or other viral factors secreted from CCHFV infected moDC cells enhance the entry of CCHFV contrary to HAZV. We have shown that CCHFV and HAZV early in infection use different strategies for entry. The data presented in this study also highlight the important role of cytokines in CCHFV-host cell interaction.

The genes to Covid-19 suceptibility

COVID-19 is affecting people in very different ways. Among this variability in the susceptibility to COVID-19 some infected people will remain non-symptomatically affected or if they have symptoms, these will be very slight. In other viral infections, the existence of genetic polymorphisms that modify the susceptibility to viral infection and its symptoms has been demonstrated. In the case of COVID-19, genetic polymorphisms have also been identified in different proteins related to the interaction and internament of COVID-19 in the host cell. These genetic polymorphisms identified as single nucleotide polymorphism in genes encoding proteins such as ACE1, ACE2, CD140 or TMPRS have already been associated with greater ease of the virus to infect the cell, but also for infection resistance. It is evident that, the genetic variability of the proteins related to the COVIDS-19-host cell interaction is important, however, it could be also important the existence of genetic polymorphisms located in genes related to the pathological consequences promoted by COVID-19 infection, such as genes related to the thrombo-coagulation system or the inflammatory response. In addition, the influence of other factors including life-style, physical exercise but also co-morbidities may modely genetic-mediated COVID-19 infection.

The Battle with COVID-19: Insight on External Intervention and Future Vaccination

The battle against the pandemic novel coronavirus infection (namely COVID-19) that gravely hurts human health is a global mission for all humanity. Currently, there are no specific COVID-19 therapies; immune-suppressors as corticosteroids, protease inhibitor antivirals, monoclonal antibody analogues as well as prospective plasma therapy. Because of the possible adverse effects and continuous emerging doubts about the drugs combating COVID-19; certain medicinal plants and dietary herbs are potentially used to prevent or cure COVID-19. Nowadays investigations and clinical trials focused on development of safe and effective either drugs or vaccines to control even stop COVID-19 in near future. Providing comprehensive spotlights on virus pathogenesis, host cell interaction, immunological response, potential therapy, and vaccine emergence for COVID-19 is discussed in this article.