Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus

Kleine-Weber, Hannah; Schroeder, Simon; Krüger, Nadine; Prokscha, Alexander; Naim, Hassan Y.; Müller, Marcel A.; Drosten, Christian; Pöhlmann, Stefan; Hoffmann, Markus

doi:10.1080/22221751.2020.1713705

Cited by 83 publications

(86 citation statements)

References 59 publications

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“…The most important of these is a glutamine at position 493 at the receptor binding domain, which explains its increased transmissibility compared to SARS CoV [27]. b) Changes in ACE-2 Receptor: With regard to MERS-CoV, which employs CD26 (DPP-4) as its receptor for cellular entry, there are naturally-occurring polymorphisms in DPP4 that impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients [28]. There is a possibility that similar variations or polymorphisms in ACE-2 could affect the viral entry and disease course.…”

Section: Role Of Renin Angiotensin System and Its Inhibitors In Sars mentioning

confidence: 99%

Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers

Singh

Gupta

Misra

2020

Diabetes & Metabolic Syndrome: Clinical Research & Revi

206

156

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a b s t r a c tBackground and aims: COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). Methods: We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. Results: From the pooled data of all ten available Chinese studies (n ¼ 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. Conclusion: Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.

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Section: Role Of Renin Angiotensin System and Its Inhibitors In Sars mentioning

confidence: 99%

Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers

Singh

Gupta

Misra

2020

Diabetes & Metabolic Syndrome: Clinical Research & Revi

206

156

View full text Add to dashboard Cite

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“…In this way, apart from pre-existing health conditions potentially predisposing to SARS-CoV-2 (e.g. obesity, hypertension, chronic respiratory disease, compromised immune status), we believe that there might be some protecting or predisposing genetic variants in genes such as ACE2, TMPRSS2 and DPP4, recently described as potentially modulating COVID-19 illness [7][8][9][10].…”

Section: Cohort Studies Of Convalescent Sars-cov Patients Revealed Thmentioning

confidence: 99%

COVID-19 experience: first Italian survey on healthcare staff members from a Mother-Child Research Hospital using combined molecular and rapid immunoassays test

Comar

Brumat

Concas

et al. 2020

Preprint

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The fast spread of the novel coronavirus (SARS-CoV-2) has become a global threat hitting the worldwide fragile health care system. In Italy, there is a continued COVID-19 growth of cases and deaths that requires control measures for the correct management of the epidemiological emergency. To contribute to increasing the overall knowledge of COVID-19, systematic tests in the general population are required.Here, we describe the first Italian survey performed in 727 employees belonging to a Mother-Child Research hospital tested for both viral (nasopharyngeal and oropharyngeal swabs) and antibody presence. Individuals were divided into three risk categories (high, medium and low) according to their job activity. Only one subject was positive at the swab test while 17.2% of the cohort was positive for the presence of antibodies. Results highlighted that the presence of Positive antibodies is significantly associated with high and medium risk exposure occupation (p-value=0.026) as well as cold and conjunctivitis symptoms (p-value=0.016 and 0.042 respectively). Moreover, among healthcare professionals, the category of medical doctors showed a significant association with the presence of antibodies against SARS-CoV-2 (p-value=0.0127). Finally, we detected a rapid decrease in antibody intensity between two assessments performed within a very short period (p-value=0.009). Overall, the present study increases our knowledge of the epidemiological data of COVID-19 infection in Italy, suggesting a high prevalence of immune individuals (i.e. at least among at-risk categories) and the efficacy of the combined diagnostic protocol to monitor the possible outbreak.

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“…After attachment of MRES-CoV spike (S) glycoprotein to DPP4 positive human cells the S protein undergoes proteolytic activation through the cellular serine protease TMPRSS2 and cysteine protease cathepsin L once inside endosomes 60 . It was recently reported that among fourteen characterized mutants forms of DPP4, four polymorphisms (K267E, K267N, A291P and D346-348) strongly reduce the binding and penetration of MERS-CoV into target cells and the viral replication 61 .…”

Section: If the Sars-cov-2 Like Ancestral Virus From Bats Can Meet Anmentioning

confidence: 99%

Can ACE2 receptor polymorphism predicts species susceptibility to SARS-CoV-2?

Devaux

Pinault

Osman

et al. 2020

Preprint

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A novel severe acute respiratory syndrome coronavirus named SARS-CoV-2, emerged in China in December 2019 and recently spread worldwide causing more than 144,987 deaths from COVID-19 disease. Similar to SARS-CoV that was related to a bat-borne coronavirus, this new virus originated from Rhinolophus affinis bats. Because bats usually transmit their coronaviruses to intermediate animal hosts that in turn represent a source of virus able to cross the species barrier to finally infect humans, the identification of an intermediate animal reservoir was recently the subject of intense researches. At the very beginning it was claimed that a reptile (Ophiophagus hannah) was the intermediate host. This hypothesis was quickly eliminated to be replaced by the pangolin (Manis javanica) hypothesis. Yet, several other animal species were recently reported as possible intermediate hosts in between bats and humans. To determine which intermediate animal host could have infected the index case patient with SARS-CoV-2, we used multi-sequence alignment, 3-D structure analysis and electrostatic potential surface generation of the angiotensin I converting enzyme 2 (ACE2) that serves as cellular receptor for SARS-CoV-2. We report evidence that such in silico investigation is a powerful tool that may help identification of potential SARS-CoV-2 susceptible species and that positions K31and Y41 in the a1 ridge, N82 and N90 in the loop and a3 and K353 in loop and b5 play a major role for SARS-CoV-2 binding to ACE2.

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Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus

Cited by 83 publications

References 59 publications

Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers

Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers

COVID-19 experience: first Italian survey on healthcare staff members from a Mother-Child Research Hospital using combined molecular and rapid immunoassays test

Can ACE2 receptor polymorphism predicts species susceptibility to SARS-CoV-2?

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