Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases.

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in the genome of this virus. S, M, H, and E proteins are structural proteins, and NSPs include accessory and replicase proteins. The structural and NSP components of SARS-CoV-2 play an important role in its infectivity, and some of them may be important in the pathogenesis of chronic diseases, including cancer, coagulation disorders, neurodegenerative disorders, and cardiovascular diseases. The SARS-CoV-2 proteins interact with targets such as angiotensin-converting enzyme 2 (ACE2) receptor. In addition, SARS-CoV-2 can stimulate pathological intracellular signaling pathways by triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, and Eph receptors, which play important roles in the progression of neurodegenerative diseases like Alzheimer's disease, epilepsy, and multiple sclerosis, and multiple cancers such as glioblastoma, lung malignancies, and leukemias. Several compounds such as polyphenols, doxazosin, baricitinib, and ruxolitinib could inhibit these interactions. It has been demonstrated that the SARS-CoV-2 spike protein has a stronger affinity for human ACE2 than the spike protein of SARS-CoV, leading the current study to hypothesize that the newly produced variant Omicron receptor-binding domain (RBD) binds to human ACE2 more strongly than the primary strain. SARS and Middle East respiratory syndrome (MERS) viruses against structural and NSPs have become resistant to previous vaccines. Therefore, the review of recent studies and the performance of current vaccines and their effects on COVID-19 and related diseases has become a vital need to deal with the current conditions. This review examines the potential role of these SARS-CoV-2 proteins in the initiation of chronic diseases, and it is anticipated that these proteins could serve as components of an effective vaccine or treatment for COVID-19 and related diseases. Video Abstract.

A cellular and molecular biology-based update for ivermectin against COVID-19: is it effective or non-effective?

Despite community vaccination against coronavirus disease 2019 (COVID-19) and reduced mortality, there are still challenges in treatment options for the disease. Due to the continuous mutation of SARS-CoV-2 virus and the emergence of new strains, diversity in the use of existing antiviral drugs to combat the epidemic has become a crucial therapeutic chance. As a broad-spectrum antiparasitic and antiviral drug, ivermectin has traditionally been used to treat many types of disease, including DNA and RNA viral infections. Even so, based on currently available data, it is still controversial that ivermectin can be used as one of the effective antiviral agents to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not. The aim of this study was to provide comprehensive information on ivermectin, including its safety and efficacy, as well as its adverse effects in the treatment of COVID-19.

Hypoxia-inducible factor 1 alpha (HIF-1α) stimulated and P2X7 receptor activated by COVID-19, as a potential therapeutic target and risk factor for epilepsy.

Based on available evidence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a neuroinvasive virus. According to the centers for disease control and prevention (CDC), coronavirus disease 2019 (COVID-19) may cause epilepsy. In this line, COVID-19 can stimulate hypoxia-inducible factor-1 alpha (HIF-1α) and activate P2X7 receptor. Both HIF-1α and P2X7 receptors are linked to epileptogenesis and seizures. Therefore, in the current study, we suggested that COVID-19 may have a role in epileptogenesis and seizure through HIF-1α stimulation and P2X7 receptor activation. Consequently, pharmacological targeting of these factors could be a promising therapeutic approach for such patients.

Possible role of autophagy induced by COVID-19 in cancer progression, chemo-resistance, and tumor recurrence.

COVID-19 infection is a serious threat to patients with primary diseases, especially multiple cancers. Studies suggest that cancer patients are one of the most susceptible populations to experience severe COVID-19 and death. In addition, a number of studies suggest various mechanisms for SARS-CoV-2 in cancer progression. In this study, we discussed the role of SARS-CoV-2 in the induction of autophagy and we hypothesized that autophagy induced by COVID-19 not only can contribute to viral replication but also potentially can lead to cancer progression, chemo-resistance, and tumor recurrence in multiple cancer patients. Therefore, targeting autophagy-related signaling pathways and cellular and molecular processes could be a potentially promising therapeutic approach for cancer patients with COVID-19. Hence, this study can shed light on a new window on the management of such patients. However, more investigations in the future are required to understand other pathological effects of COVID-19 infection on cancer patients to provide new therapeutic strategies to combat these complications in these patients.

The roles of Eph receptors, neuropilin-1, P2X7, and CD147 in COVID-19-associated neurodegenerative diseases: inflammasome and JaK inhibitors as potential promising therapies.

The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy and effective vaccine is critical to overcoming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes of SARS-CoV-2 may help propose antiviral drugs and novel vaccines. Several receptors have been demonstrated for the interaction of spike (S) protein of SARS-CoV-2 with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands and Eph receptors, neuropilin 1 (NRP-1), P2X7, and CD147. The expression of these entry receptors in the central nervous system (CNS) may make the CNS prone to SARS-CoV-2 invasion, leading to neurodegenerative diseases. The present review provides potential pathological mechanisms of SARS-CoV-2 infection in the CNS, including entry receptors and cytokines involved in neuroinflammatory conditions. Moreover, it explains several neurodegenerative disorders associated with COVID-19. Finally, we suggest inflammasome and JaK inhibitors as potential therapeutic strategies for neurodegenerative diseases.