The Origin, Transmission, and Clinical Therapies in the Management of Coronavirus Diseases
A brief history of the human coronaviruses (HCoVs) tells us that they are inherently zoonotic in origin. The molecular analysis of these HCoVs revealed a large genome of approximately 30 kb that encodes for a fixed subset of structural proteins, non-struc
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The Origin, Transmission, and Clinical Therapies in the Management of Coronavirus Diseases Nagham Kaka, Aman Pal, Sora Abdul-Fattah, and Pramath Kakodkar Abstract A brief history of the human coronaviruses (HCoVs) tells us that they are inherently zoonotic in origin. The molecular analysis of these HCoVs revealed a large genome of approximately 30 kb that encodes for a fixed subset of structural proteins, non-structural proteins, and varied accessory proteins. Additionally, the HCoV genomes have a prerequisite ability to undergo mutation and recombination that fosters advantageous gene gain and gene losses. A culmination of all these factors has led to the evolution of HCoVs that can cause mild infections as well as the global pandemic COVID-19. Using simplified phylogenetic trees, we elucidate the probable primary zoonotic origin and the animal reservoirs for the HCoV family. This chapter aims to highlight the evolution of the common cold triggering HCoV cluster (HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1), as well as the severe epidemic and pandemic causing HCoV cluster (SARS-CoV-1, SARS-CoV-2, and MERS-CoV). The final section of this chapter is dedicated to exploring clinical therapies against the above CoVs. As such the CoV replication pathways are exploited, and a select few repurposed drug candidates, novel agents, and their combination are organized based on the steps they inhibit in this pathway. Key words COVID-19, Human coronaviruses (HCoVs), Main protease (Mpro), Remdesivir, Lopinavir-ritonavir, Umifenovir (Arbidol), Favipiravir, Hydroxychloroquine, Camostat mesylate
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Introduction The HCoV responsible for the COVID-19 global pandemic is designated as SARS-CoV-2. In hopes to reduce the number of cases and understand its evolution, the research into the CoV genome has expanded rapidly. In an era of high-throughput sequencing, there is a large repository of complete genomes for each of the HCoVs. Analyses of these genomes for identifying the subtleties in their conserved and non-conserved regions enable researchers to bootstrap high similarity relationships between these HCoVs. These similarities can be clustered and are schematically represented into phylogenetic trees. The initial part of this chapter aims at tracing the primary zoonotic origin and animal reservoir for some select HCoV. Learning about their respective origins and reservoirs allows for a deeper understanding of the
Nagham Kaka et al.
HCoV genomic evolution and the similarities that reside between each HCoV genome. Furthermore, the transmission of these HCoVs will also be reviewed to understand the different modes of spread. The HCoVs are respiratory viruses, and their primary mode of transmission is via person-person respiratory droplets. This was notable in the cases of severe acute respiratory syndrome coronaviruses (SARS-CoV-1 and SARS-CoV-2), but the Middle Eastern respiratory syndrome coronavirus (MERS-CoV) demonstrated limited person-person transmission. The most common source of MERSCoV transmission was proven to be human-c
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