10.1016/j.cytogfr.2020.06.013 [PMC free content] [PubMed] [CrossRef] [Google Scholar] Gonzlez\Pacheco, H. , Amezcua\Guerra, L. provides triggered the coronavirus disease\19 (COVID\19) pandemic internationally (Sahin et al.,?2020; Wang, Hu, et al.,?2020), and provides resulted in severe harm to individual lives as well as the economy greater than 200 countries worldwide. By the proper period this manuscript is certainly posted, 143,445,675 folks have been contaminated by this pathogen, as well as the loss of life toll mounts up to 3,051,736 internationally (World Health Firm internet site, n.d.). Besides SARS\CoV\2, six even more coronaviruses have already been characterized by today: individual CoV229E (HCoV\229E, 1966), individual CoV OC43 (HCoV\OC43, 1967), individual CoV HKU1 (HCoV\HKU1, 2004), individual CoV NL63 (HCoV\NL63, 2004), serious severe respiratory symptoms CoV (SARS\CoV, 2003), and Middle East respiratory symptoms CoV (MERS\CoV, 2013). Chronological evaluation from the commence period and severity of the viruses shows that the outbreak routine from the coronaviruses gets shorter and shorter, as well as the impact from the viruses gets worse and worse. To take care of current SARS\CoV\2 infections, and moreover to get ready for unforeseeable brand-new coronaviruses in the future, scientists from the globe respond quickly in attempt to identify suitable solutions such as small molecules for the potential therapy or vaccines for the prevention. SARS\CoV\2 belongs to a class of coronaviruses featured with positive\sense, enveloped, single\stranded RNA (Zeidler & Karpinski,?2020). The spike proteins (S proteins) on the viral envelope include two subunits, S1 and S2, which are the Rabbit polyclonal to AMPKalpha.AMPKA1 a protein kinase of the CAMKL family that plays a central role in regulating cellular and organismal energy balance in response to the balance between AMP/ATP, and intracellular Ca(2+) levels. key surface proteins that participate in the interaction between the viruses and the host cells, and eventually promote the virus to enter the host cell (Walls et al.,?2020).SARS\CoV\2 uses angiotensin\converting enzyme 2 (ACE2) receptors to enter the lung cells (Figure?1a). After the attachment of the virus to the host cells, the S protein of the virus interacts with protease enzymes from the host cells, enabling the virus fusing to the host cell membrane (Cascella et al.,?2021). This process relies on transmembrane serine protease (TMPRSS2) activating S proteins (Hoffmann et al.,?2020; Valencia,?2020). After the genomic RNA released into the cytoplasm and then translated to produce polyproteins, which is Tenovin-3 facilitated by virally encoded chymotrypsin\like protease (3CLpro) or main protease (Mpro) (Cascella et al.,?2021). Polyproteins cleavage affords non\structural Tenovin-3 proteins for the viral RNA replicase\transcriptase complex. Viral nucleocapsids are assembled with the structural proteins after the viral replication and transcription. Upon encasing viral RNA, these nucleocapsids form the new virions and are then released from the cells via exocytosis (Valencia,?2020). Clinical studies indicate that several cytokines from severe patients’ tissue undergo extensive changes, which play a crucial role in the COVID\19 pathogenesis (Liu, Zhang, Huang, Yang, et al.,?2020; Mehta, McAuley, et al.,?2020; Wan et al.,?2020). Hypercytokinemia (also known as cytokine storm) may play as Tenovin-3 a pivotal role in life\threatening pathological processes (Figure?1b) (Xu, Shi, Li, & Zhou,?2020; Xu, Shi, Wang, et al.,?2020). It has been proven that CD4+ T cells are rapidly activated to secret inflammatory cytokines upon the infection with SARS\CoV\2, which further lead to CD14+ CD16+ monocyte activation with high interleukin expression (such as IL\1, IL\6 etc. see Figure?1b) (Zhou, Fu, et al.,?2020). Thus, blocking the IL\1 or the IL\6 receptors could potentially alleviate immunopathology caused by SARS\CoV\2. The pulmonary renin\angiotensin system (RAS) is composed by two pathways, whose balance is crucial for pulmonary homeostasis (Figure?1c). Angiotensin II (Ang II), generated by endothelial ACE, acts on angiotensin II receptor type 1 (AT1) to promote pro\inflammatory effects and vasoconstriction, whereas epithelial ACE2 cleaves Ang II into Ang (1C7), which acts on the MAS1 (MAS proto\oncogene) oncogene to exert anti\inflammatory and vasodilatory effects. The ACE\dependent Ang II formation is a vital pathophysiological mechanism in different forms of acute respiratory distress syndrome (ARDS) (South et al.,?2020). Open in a separate window FIGURE 1 (a) Schematic illustration of the replication cycle of SARS\CoV\2 and the biological targets for the potential treatment. (b) the inhibition of excessive inflammatory response. (c) SARS\CoV\2 infects type II alveolar epithelial cells (type II AEC) via the interaction between its S proteins and the ACE2 receptor.