Post – covid era: the new and unknown field

Cell biology of viral infection and COVID-19 antiviral drugs Pero Lučin Department of Physiology and Immunology, University of Rijeka Faculty of Medicine, Rijeka, Croatia Viruses are intracellular pathogens that take advantage of host-cell machinery to establish infection and replication niches within infected cells. The infection establishment is associated with the passage through the plasma membrane, unpackaging of virions, and delivery of viral nucleic acid, either RNA or DNA, at the site of viral nucleic acid transcription and replication. The entry of a virus into infected cells requires the exploitation of host-cell membranous organelle machinery to overcome the physical barrier for unpackaging of viral capsid into the cytosol. Unpacked capsids release viral nucleic acid, which initiates the viral reproduction cycle either in the cytosol or in the nucleus, where a complex replication compartment is being established. For reproduction in the cytosol, viruses exploit cytosolic components of the host cell and membranous organelles to develop replication niches. For reproduction in the nucleus, viruses should shut off host-cell processes and retain some cellular processes required to establish the replication compartment. Upon replication, newly formed capsids again exploit host-cell processes for transportation to the site of final envelopment and the egress of nascent virions from the infected cell to ensure the spread of infection. Thus, both cytoplasmic and nuclear replicating viruses interfere and exploit host cell machinery, including a considerable number of host-cell components organized into networks that execute complex integrated functions. For example, just for entry and final envelopment processes, viruses can potentially interfere with products of more than three thousand cellular genes. Thus, understanding the cell biology of these interactions is a huge task and requires understanding the host-cell cellular physiology to identify potential targets that can be exploited by products of virus-encoded genes. Consequently, understanding virus-host cell interactions is a prerequisite for identifying potential targets for antiviral interventions, including the development of antiviral drugs and antiviral therapies. This presentation will focus on the cell biology of the SARS-CoV-2 virus, a relatively small RNA virus that replicates in the cytoplasm, and cytomegalovirus (CMV), one of the largest viruses that replicate in the nucleus and establish the most complex interactions with host-cell physiological networks. The basic organization of the SARS-CoV-2 and CMV replication cycle will be presented with the particular focus on the utilization of membranous-organelle machinery for the establishment of infection, development of the replication niches, final envelopment of the nascent virions, and virion egress for the spread of infection. In addition to the classical cell biology approaches, the particular focus will be on the systemic approaches in understanding membranous organelle utilization and host-cell remodeling, including recent spatial proteomics and recycelome studies. Accordingly, the potential sites and efforts of antiviral interventions using small-molecule antiviral drugs will be discussed.