Harnessing host–virus evolution in antiviral therapy and immunotherapy

Abstract

Pathogen resistance and development costs are major challenges in current approaches to antiviral therapy. The high error rate of RNA synthesis and reverse‐transcription confers genome plasticity, enabling the remarkable adaptability of RNA viruses to antiviral intervention. However, this property is coupled to fundamental constraints including limits on the size of information available to manipulate complex hosts into supporting viral replication. Accordingly, RNA viruses employ various means to extract maximum utility from their informationally limited genomes that, correspondingly, may be leveraged for effective host‐oriented therapies. Host‐oriented approaches are becoming increasingly feasible because of increased availability of bioactive compounds and recent advances in immunotherapy and precision medicine, particularly genome editing, targeted delivery methods and RNAi. In turn, one driving force behind these innovations is the increasingly detailed understanding of evolutionarily diverse host–virus interactions, which is the key concern of an emerging field, neo‐virology. This review examines biotechnological solutions to disease and other sustainability issues of our time that leverage the properties of RNA and DNA viruses as developed through co‐evolution with their hosts.

Thapsigargin at Non-Cytotoxic Levels Induces a Potent Host Antiviral Response that Blocks Influenza A Virus Replication

“…The problem of drug resistance faced by current and near-market antivirals is a serious concern, as exemplified by the alarming emergence of resistance to the recently approved antiviral baloxavir marboxil (Xofluza) [ 2 , 36 , 37 ]. Targeting the virus proteins directly applies a strong selection pressure for the emergence of drug-resistance escape mutants [ 38 , 39 ]. Host-dependent therapies are a potential alternative to targeting the virus proteins directly and are not readily overcome by the highly mutable influenza virus [ 5 ].…”

Immunosuppression and cardiovascular dysfunction in patients with severe versus mild coronavirus disease 2019: a case series

“…As a result of the unique immunosuppressive capacity of MSCs, serum levels of proinflammatory cytokines and chemokines were significantly reduced after their administration, thus reducing monocytes and macrophages in the fragile lung. 39,40 In conclusion, our study suggests that infection with SARS-CoV-2 tends to affect not only the respiratory system, but also the immune and cardiovascular systems. Therefore, patients with COVID-19 must be carefully monitored for immune system damage and cardiac events.…”

Network analysis, sequence and structure dynamics of key proteins of coronavirus and human host, and molecular docking of selected phytochemicals of nine medicinal plants

“…The structures of these proteins were obtained from PDB database (www.rcsb.org/pdb) in pdb format and 3DLigandSite server (http://www.sbg.bio.ic.ac.uk/3dligandsite/advanced.cgi, Wass et al, 2010), was used to predict the active site amino acid residues of the protein targets. The structures of selected 10 predicted drugs from the expression network (Chen et al, 2012;Lamb et al, 2006), five (5) drugs for repurposing as anti-nCoV (Pang et al, 2020;Hosseini & Amanlou, 2020;Gordon et al, 2020;Ugboko et al, 2019;De Clercq, 2006) and seventeen (17) selected phytochemicals from 9 medicinal plants (selected from Table 1, based on overall constituents including ellagic acid and caffeic acid which are key inhibitors of multifunctional proteins in the human host of SARS-CoV-2), were obtained from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/) in sdf format and were converted to pdb format using PyMol v2.0.7. The crystal structure of the seven (7) protein targets were prepared for docking by removing all water molecules, multichain, and heteroatoms using PyMol v2.0.7.…”

“…Studies have enumerated the proteins in CoV that could be effective drug targets to include: 3 C-like protease (3CL pro ), RNA-dependent RNA polymerase, and RNA helicase for viral replication and transcription (Xu et al, 2020;Chen et al, 2020;Tong, 2009;Ziebuhr et al, 2000). Computational techniques such as virtual screening, molecular docking and dynamic simulations, have been employed to predict potential drug for SARS-CoV (Hosseini & Amanlou, 2020;Beck et al, 2020;Nukoolkarn et al, 2008). Comparative analysis of 28 protein sequences SARS-CoV-2 and SARS-CoV by Xu et al (2020), showed percent identity between 68.37% (nsp2) to 99.83% (helicase).…”

“…Host-oriented approaches for identification and development of potential drug compounds often provide a broad list of potential therapeutic targets when compare to the gene products obtainable from most human-infective RNA viruses (Atkinson et al, 2018). The inherent dependency of virus on multifunctional proteins of their host for several crucial replication steps causes susceptibilities that may be leverage upon for discovery of useful antiviral drugs, and by restricting availability of such host proteins to the virus may interrupt the overall replication mechanisms (Heaton, 2019).…”