Angiotensin-(1-7) for COVID-19

The renin-angiotensin system (RAS) plays a central role in regulating blood pressure and cardiovascular health. Angiotensin-converting enzyme (ACE) facilitates the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that contributes to hypertension and heart failure. Conversely, ACE2 converts angiotensin II into angiotensin-(1-7), a vasodilator with protective cardiovascular effects. An imbalance between ACE and ACE2 activities has been increasingly associated with the progression of cardiovascular diseases and complications related to COVID-19. This review analyzed 100 relevant studies published up to May 2024, identified through a comprehensive literature search on PubMed and Scopus. The findings highlighted that dysregulation of the ACE/ACE2 axis exacerbates cardiovascular dysfunction. The interaction of SARS-CoV-2 with ACE2 reduces its protective function, intensifying inflammatory responses and leading to complications such as lung injury and heart failure. Additionally, genetic polymorphisms in ACE and ACE2 influence individual susceptibility and severity of COVID-19. Promising therapeutic strategies, including ACE2-based peptides and angiotensin II receptor modulators, are under investigation but require further clinical validation. Targeting the ACE/ACE2 axis could provide effective treatment options for cardiovascular disease and COVID-19-related complications, warranting further in-depth research.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected all of humanity since the first case was reported and spread rapidly around the world, creating a pandemic. Despite the repurposing of many drugs and the development of vaccines, effective treatment and protection are limited. In addition, SARS-CoV-2 continues to be a current public health problem with complications, identifying cases of long-term Covid syndrome, and detection of vaccine-related adverse events. It can be said that the most important factor underlying all these problems is that the interaction between SARS-CoV-2 and renin-angiotensin-aldosterone system (RAAS) is not completely understood despite extensive research. Although different disciplines have limited determinations from their own perspectives regarding the communication with RAAS, it has not been sufficiently expressed in a way to see the whole picture. In this study, it is tried to see the whole picture in the interaction of RAAS and SARS-CoV-2. It is detected inadequacies in treatments and interactions that may be design errors in vaccines. These determinations also show that our templates for producing treatments are not sufficient. For this reason, we have to develop our templates with what we have learned specifically about SARS-CoV-2. Considering the accuracy of our hypothesis on the SARS-CoV-2 - RAAS relationship, Ang(1-7) can be considered a strong option for treatment. Although the SARS-CoV-2 pandemic seems to be over, epidemics and even new pandemics are likely to occur with new mutations.

Viruses with rapid replication and easy mutation can become resistant to antiviral drug treatment. With novel viral infections emerging, such as the recent COVID-19 pandemic, novel antiviral therapies are urgently needed. Antiviral proteins, such as interferon, have been used for treating chronic hepatitis C infections for decades. Natural-origin antimicrobial peptides, such as defensins, have also been identified as possessing antiviral activities, including direct antiviral effects and the ability to induce indirect immune responses to viruses. To promote the development of antiviral drugs, we constructed a data repository of antiviral peptides and proteins (DRAVP). The database provides general information, antiviral activity, structure information, physicochemical information, and literature information for peptides and proteins. Because most of the proteins and peptides lack experimentally determined structures, AlphaFold was used to predict each antiviral peptide’s structure. A free website for users (http://dravp.cpu-bioinfor.org/, accessed on 30 August 2022) was constructed to facilitate data retrieval and sequence analysis. Additionally, all the data can be accessed from the web interface. The DRAVP database aims to be a useful resource for developing antiviral drugs.