RESUMEN
The COVID-19 pandemic affected millions of people worldwide, becoming a challenge of every nation. Since the COVID-19 can present wide spectrum of clinical signs and symptoms, patients with symptoms similar to that of COVID-19 may be misdiagnosed during the context of COVID-19 pandemic. In this regard, various co-infections may affect the outcome of COVID-19 patients if it lefts undiagnosed, especially during the administration of immunosuppressive drugs. Similar to COVID-19, TB affect the lungs and respiratory airways primarily. These two diseases have resembling symptoms, including dry cough, fever, and dyspnea. Due to the importance of early COVID-19 diagnosis, many other respiratory infectious diseases such as tuberculosis (TB) may be missed. Herein, a case of COVID-19 and tuberculosis co-infection is presented.
RESUMEN
BACKGROUND: Hypertension has been identified as the most common comorbidity in coronavirus disease 2019 (COVID-19) patients, and has been suggested as a risk factor for COVID-19 disease outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host human cells via binding to host cell angiotensin-converting enzyme 2 (ACE2) receptors. Inhibition of ACE2 has been proposed as a potential therapeutic approach to block SARS-CoV-2 contagion. However, some experts suggest that ACE2 inhibition could worsen the infection. Here, we aimed to study the effect of ACE2 inhibition on the SARS-CoV-2 spike protein binding to ACE2. METHOD: Crystallographic structures of the SARS-CoV-2 spike protein, the spike receptor-binding domain, native ACE2, and the ACE2 complexed with MLN-4760 were used as the study model structures. The spike proteins were docked to the ACE2 structures and the dynamics of the complexes, ligand-protein, and protein-protein interactions were studied by molecular dynamics simulation for 100âns. RESULTS: Our result showed that inhibition of ACE2 by MLN-4760 increased the affinity of the SARS-CoV-2 spike protein binding to ACE2. Results also revealed that spike protein binding to the ACE2 inhibited by MLN-4760 restored the enzymatic active conformation of the ACE2 from closed/inactive to open/active conformation by removing MLN-4760 binding from the ligand-binding pocket of ACE2. CONCLUSION: We conclude that using ACE2 inhibitors can increase the risk of SARS-CoV-2 infection and worsen COVID-19 disease outcome. We also found that the SARS-CoV-2 can abrogate the function of ACE2 inhibitors and rescue the enzymatic activity of ACE2. Therefore, ACE2 inhibition is not a useful treatment against COVID-19 infection.