scholarly journals Human Cell Receptors and Downstream Cascades: A Review of Molecular Aspects and Potential Therapeutic Targets against COVID-19

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Shervin Afzali ◽  
Mohammadvala AshtarNakhaei ◽  
Sara Shiari ◽  
Afshan Shirkavand ◽  
Shirin Farivar

Context: There have been two coronavirus-related pandemics during the past 18 years, including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV in 2002 and 2012, respectively. Seven years after the emergence of MERS, a new coronavirus (i.e., SARS-CoV-2) was detected in several patients in 2019. SARS-CoV-2 spread widely, and its high prevalence enabled the virus to start a new pandemic in 2020. It is believed that the higher infectivity of the virus in comparison to that of SARS-CoV is related to its molecular interaction affinity of transmembrane spike glycoprotein and human angiotensin-converting enzyme 2 (ACE-2) cell receptors. Moreover, the primary reason for the high case fatality rate (CFR) is the cytokine storm and acute respiratory distress syndrome (ARDS) because of the immune system response to the invaders. Hence, a solid understanding of the components involved in the mechanism of viral entry and immune system response is crucial for finding approaches to disrupt the virus interplay and neutralizing its impacts on the host immune system. In this review, we investigated the molecular aspect and potential therapeutic targets associated with cell receptors and downstream signaling cascades. Evidence Acquisition: In this review, we presented the available information regarding the coronavirus disease 2019 (COVID-19). A systematic search was implemented on several online databases, including Google Scholar, PubMed, and Scopus during 2019-2021 using the following keywords: "SARS-CoV-2", "COVID-19", "ACE-2", "Therapeutic Targets", "Acute respiratory distress syndrome", and "Cytokine Storm". Results: Various internal or external agents are responsible for the virus infectivity and stimulating acute immune system response. Since currently there is no cure for the treatment of COVID-19, several repurposed drugs can be employed to disrupt the process of viral entry and mitigate the symptoms raised by the cytokine storm. Inhibition of several agents, including signal transduction mediators and TMPRSS2 may be momentous. Conclusions: Despite the increase in the CFR, no drugs were developed with significant efficacy. Understanding the virus entry mechanism and the immune system’s role could help us surmount the problems in developing a promising drug or employing the repurposed ones.

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ji Hoon Jang ◽  
Hang Jea Jang ◽  
Hyun-Kuk Kim ◽  
Jin Han Park ◽  
Hyo-Jung Kim ◽  
...  

Abstract Background Inhalation injury from smoke or chemical products and carbon monoxide poisoning are major causes of death in burn patients from fire accidents. Respiratory tract injuries from inhalation injury and carbon monoxide poisoning can lead to acute respiratory distress syndrome and cytokine storm syndrome. In the case of acute respiratory failure needing mechanical ventilation accompanied by cytokine storm, mortality is high and immediate adequate treatment at the emergency department is very important. Case presentation This report describes a case of acute respiratory distress syndrome and cytokine storm followed by carbon monoxide poisoning in a 34-year-old Korean male patient who was in a house fire, and was successfully treated by extracorporeal membrane oxygenation and direct hemoperfusion with polymyxin B-immobilized fiber column at emergency department. Conclusions To prevent mortality in acute respiratory distress syndrome with cytokine storm from inhalation injury and to promote a better prognosis, we suggest that early implication of extracorporeal membranous oxygenation along with direct hemoperfusion with polymyxin B-immobilized fiber column even at the emergency department should be considered.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Braira Wahid ◽  
Noshaba Rani ◽  
Muhammad Idrees

Abstract After wreaking havoc on a global level with a total of 5,488,825 confirmed cases and 349,095 deaths as of May 2020, severe acute respiratory syndrome coronavirus 2 is truly living up to the expectations of a 21st-century pandemic. Since the major cause of mortality is a respiratory failure from acute respiratory distress syndrome, the only present-day management option is supportive as the transmission relies solely on human-to-human contact. Patients suffering from coronavirus disease 2019 (COVID-19) should be tested for hyper inflammation to screen those for whom immunosuppression can increases chances of survival. As more and more clinical data surfaces, it suggests patients with mild or severe cytokine storms are at greater risk of failing fatally and hence these cytokine storms should be targets for treatment in salvaging COVID-19 patients.


2020 ◽  
Vol 5 (3) ◽  
pp. 197-201 ◽  
Author(s):  
Hesam Khodadadi ◽  
Évila Lopes Salles ◽  
Abbas Jarrahi ◽  
Fairouz Chibane ◽  
Vincenzo Costigliola ◽  
...  

2020 ◽  
Vol 183 (5) ◽  
pp. R133-R147 ◽  
Author(s):  
John P Bilezikian ◽  
Daniel Bikle ◽  
Martin Hewison ◽  
Marise Lazaretti-Castro ◽  
Anna Maria Formenti ◽  
...  

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.


2020 ◽  
pp. 004947552097142
Author(s):  
Abraham M Ittyachen

The majority of patients with Covid-19 have a good outcome. However, complications principally of acute respiratory distress syndrome (ARDS) and multiple-organ failure can occur rapidly. Leptospirosis, a zoonotic disease, is similar to Covid-19 in that most infections are mild or asymptomatic and only a small number develop ARDS. Cytokine storm is considered to be the main incriminating factor in both. High dose steroids have been used to ameliorate the effects in leptospirosis, and similarly, reports suggest a benefit in Covid-19. SARS CoV-2 and leptospira, one a virus and the other a bacterium, are two species separated by millions of years of evolution, but producing illnesses with similar spectra, with cytokine storm being the common precipitating factor. As data are accrued from around the world, more light may be shed on features analogous to both pathways.


Immunotherapy ◽  
2020 ◽  
Vol 12 (15) ◽  
pp. 1127-1132 ◽  
Author(s):  
Juan David Cala-García ◽  
Juan David Sierra-Bretón ◽  
Jorge Eduardo Cavelier-Baiz ◽  
Álvaro A Faccini-Martínez ◽  
Carlos Eduardo Pérez-Díaz

Background: Severe pneumonia and acute respiratory distress syndrome (ARDS) due to COVID-19 is a challenge for nowadays medical practice. Although there is no clarity in the principal mechanism of lung damage and ARDS development, it has been suggested that one of the main reasons of this pathology is the hyperactivation of the immune system, better known as cytokine storm syndrome. Tocilizumab has been proposed to treat COVID-19 severe cases associated to ARDS. Results & methodology: Here we present two successful cases of tocilizumab administration in two COVID-19 patients with prior administration of antiviral therapy (hydroxychloroquine, azithromycin, lopinavir and ritonavir) with adequate response and resolution of ARDS, septic shock and severe pneumonia within the first 72 h. Discussion & conclusion: This case supports the usage of tocilizumab as an effective therapy in COVID-19 associated cytokine storm syndrome. Further studies should be done in order to assess its effectiveness and security.


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