Current Protein and Peptide Science - Volume 22, Issue 10, 2021

Along with structural and non-structural proteins, SARS-CoV-2, SARS-CoV, and MERS-CoV can also express accessory proteins. During the past few years, there have been only a few studies focusing on this set of proteins. Despite available data on these proteins, there are still a lot of questions on the functions of these proteins during infection that must be answered. With these three betacoronaviruses causing outbreaks in humans during the past few years, the need for a thorough understanding of the roles of these proteins is becoming more important and relevant. This review provides a survey of the existing knowledge on the roles of these proteins during infection. In addition to current evidence, a more comprehensive view of the functions of these proteins is presented together with their potential as therapeutic targets, which were determined by using different bioinformatics platforms. This information may help test effective therapeutic regimens against these viruses and in preparing for future pandemics.

Naturally occurring peptides found in the human skin can serve particular biological activities and play roles as signaling molecules of various physiological processes such as homeostasis, growth, defense or immunity. Their great biological activity resulted in a growing interest in the pharmaceutical industry. Researchers consider peptides either promising compounds with potential application for human diagnosis, therapy or cosmetics. Peptides are becoming interesting cosmetic ingredients with the functions to reduce premature skin aging, improve the barrier function of skin, moisturize the skin, protect it from UV damage, and anti-inflammatory properties that alleviate acne and irritation. Till now, peptides of different origins were investigated in formulation developed to enhance collagen or elastin production, increase fibroblast proliferation, improve wound healing or skin condition. Most of them are obtained by chemical synthesis or by partial digestion of animal proteins. Short and easily synthesized peptides with alternative amino acid sequence, and combinations have created a new field of molecules inspired by nature and implemented in the cosmetic industry. Nowadays, peptides are cheaper and easier to produce in large quantities. The efficient process development methods allow obtaining nearly unlimited sequences, which makes them functionally preferred. Generally, cosmetic peptides are categorized as carrier peptides, neurotransmitter- affecting peptides, enzyme inhibitor peptides and signal peptides. The use of signal peptides in cosmetics increased over a few years. These molecules trigger a signaling cascade and stimulate fibroblast collagen production, the proliferation of elastin, fibronectin, laminin, etc. Thus, a literature search on a topical application of the most common signal peptides; and their current status in the cosmetic industry was carried out.

Angiotensin-converting enzyme (ACE) shares some homologies with ACE2. However, they are not inhibited by the same inhibitors, but both are associated primarily with the hypertensive disorder through the renin-angiotensin system (RAS). The principal activity of ACE2 is to metabolize Ang II into the vasodilatory Ang-(1-7). The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought the ACE2 to the center of attention. This coronavirus uses the host cell ACE2 protein to enter and infect the epithelial cells. In light of the virus's entrance into human cells, the differences in the molecular basis of ACE2 among affected patients may cause their different responses to the virus. Many details about the specific interaction between the viral S protein and ACE2 are already reported. To date, some effective clinically approved vaccines are in use globally, and many others are under development, but no effective specific therapeutic drugs are available against COVID-19. Inhibitors, especially peptide inhibitors, have a great potential to be used for the treatment of COVID-19 and other possible emerging diseases caused by viral pathogens. As a result of the well-known viral protein structures and their host cell targets such as ACE2, antiviral peptides could be appropriately designed and optimized for therapeutic purposes. A better understanding of the structure and pathophysiology of the ACE2 receptor and the interplay between the viral S protein and ACE2 may help to find the solution for the virus treatment. This review summarizes the current understanding of S protein interaction with the ACE2 protein as a potential specific target against SARS-CoV-2 and strategies using peptides against COVID-19.

Background: The role of an alloimmune response against non-self-antigens is established in organ transplantation. HLA incompatibilities are mainly responsible for this recognition between donor and recipient, but they may also be involved in the reactivity against other alloantigens expressed on the allograft resulting from an autoimmune response developed against selfantigens. Objective: Our study aimed to determine the presence of non-anti-HLA antibodies (anti-AT1R and anti-ETAR) in sera from patients with end-stage renal disease, who underwent kidney transplantation in pre- and post-transplantation samples to study their influence on the development and evolution of acute humoral rejections and DSAs. Methods: Antibodies (Abs) against two G protein-coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR), have been detected in the sera of transplant recipients, who experience allograft dysfunction, patients with coronary heart disease, marginal hypertension and refractory, vascular lesions, myocardial hypertrophy and chronic inflammatory diseases, such as atherosclerosis or sclerosis. Results: Kidney graft recipients were monitored for anti-ETAR, -AT1R, and -HLA Abs in pre-and post-transplant evolution, and anti-AT1R and/or -ETAR Abs were detected in 24% of recipients (22.4% with anti-AT1R Abs and 9.8% with anti-ETAR Abs). Due to acute humoral rejection, Graft loss was detected in 6.4% of patients with anti-GPCRs non-HLA Abs, and 3.2% had DSA anti-HLA Abs. In this research, we have described how the function of the anti-GPCRs autoAbs and how these Abs that activate GPCRs could influence graft outcome. Conclusion: In conclusion, there is a high association of non-HLA anti-GPCRs Abs levels with reduced kidney function after transplantation, especially in the presence of DSA anti-HLA Abs. Although more studies are needed, anti-AT1R and anti-ETAR antibodies may be helpful biomarkers that allow the risk of graft loss to be assessed.