The COVID-19 viral pneumonia pandemic coerced by SARScov-2 virus has swept across all countries at the beginning of 2020 in one year has already claimed more than 2 million lives. Therefore, a wide population vaccination and development of effective treatment of the decease are necessary. The paper suggest drug molecules, which are able to bind effectively with the membrane channel formed by E protein and disrupt it’s right functioning and the SARS-cov-2 virus in whole. The development of an effective drug is a task of great importance because of the ability of SARS-cov-2 virus to infect fast a large population, sometimes probably through cross-species barriers, and to mutate quickly A reasonable approach to affect and disrupt the functional cycle of the SARS-cov-2 virus particle, is to specifically affect the envelope protein E, which forms the trans-membrane channel E, an important element that ensures its proper functioning.

The E channel is formed by amino acid residues 8-65 of each of the five subunits A, B, C, D, E. The five interacting α-helices build up the E protein, which has central channel of large diameter ~17-19 Å, if measured between Cα atoms of the NMR structure, PDB code 5X29 solved at T=308K, pH=5.5, 50 mM NaCl. The channel activity of the E protein of the SARS-cov-2 coronavirus was shown to be critical for infection process of living cell. For example, pathogenicity was significantly hampered when the trans membrane segment of infectious bronchitis virus E protein was replaced with a heterologous domain that lacked ion channel activity The importance of ion channel functionality for virulence has been demonstrated in several viruses. For example, the H+ channel activity of the M2 protein of influenza A is critical for infection in two ways:  following endocytosis, the channel facilitates H+  and K+ transport into the viral lumen, enabling viral RNA to dissociate and initiate replication .

 In corona viruses, the channel activity of the E protein was shown to be critical for infectivity. It is shown that virus pathogenicity was significantly reduced when the transmembrane segment of infectious bronchitis virus E protein was replaced with a heterologous domain that lacked ion channel activity. In SARS-CoV-1 virus, studies have shown that viruses in which the channel activity of the E protein was abolished, were far less infectious. A recent computational study of interaction of SARS-CoV-2 virus with several drug molecules affecting replication cycle suggest molecular structures to inhibit the process. The structure of coronavirus protein E is the least understood in terms of mechanism of action and structure. Functionally, the E protein has been implicated in viral assembly, release, and pathogenesis  and it is crucially that E proteins are important for viral pathogenesis. The small size of E channel and overall hydrophobicity prompted suggestions that coronavirus E proteins might be functionally similar to viroporins. Indeed, E channel is small and usually hydrophobic multifunctional viral proteins that modify cellular membranes, thereby facilitating virus release from infected cells.

Best Regards,
Nancy Ella
Editor-In-Charge
Drug Designing: Open Access