The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses

Tse, Longping V.; Meganck, Rita M.; Graham, Rachel L.; Baric, Ralph S.

doi:10.3389/fmicb.2020.00658

Cited by 100 publications

(124 citation statements)

References 348 publications

(324 reference statements)

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“… Abstract Coronaviruses, including SARS-CoV-2 the etiological agent of COVID-19 disease, have caused multiple epidemic and pandemic outbreaks in the past 20 years 1–3 . With no vaccines, and only recently developed antiviral therapeutics, we are ill equipped to handle coronavirus outbreaks 4 . A better understanding of the molecular mechanisms that regulate coronavirus replication and pathogenesis is needed to guide the development of new antiviral therapeutics and vaccines.…”

mentioning

confidence: 99%

Comparative analysis of coronavirus genomic RNA structure reveals conservation in SARS-like coronaviruses

Sanders

Fritch

Madden

et al. 2020

Preprint

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27Coronaviruses, including SARS-CoV-2 the etiological agent of COVID-19 disease, have 28 caused multiple epidemic and pandemic outbreaks in the past 20 years 1-3 . With no vaccines, 29 and only recently developed antiviral therapeutics, we are ill equipped to handle coronavirus 30 outbreaks 4 . A better understanding of the molecular mechanisms that regulate coronavirus 31 replication and pathogenesis is needed to guide the development of new antiviral therapeutics 32 and vaccines. RNA secondary structures play critical roles in multiple aspects of coronavirus 33 replication, but the extent and conservation of RNA secondary structure across coronavirus 34 genomes is unknown 5 . Here, we define highly structured RNA regions throughout the MERS- 35CoV, SARS-CoV, and SARS-CoV-2 genomes. We find that highly stable RNA structures are 36 pervasive throughout coronavirus genomes, and are conserved between the SARS-like CoV. 37Our data suggests that selective pressure helps preserve RNA secondary structure in 38 coronavirus genomes, suggesting that these structures may play important roles in virus 39 replication and pathogenesis. Thus, disruption of conserved RNA secondary structures could be 40 a novel strategy for the generation of attenuated SARS-CoV-2 vaccines for use against the 41 current COVID-19 pandemic. 42 43 Main 44 Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory 45 syndrome coronavirus (MERS-CoV), and SARS-CoV-2, the etiological agent of the current 46 COVID-19 pandemic, have caused widespread disease, death, and economic hardship in the 47 past 20 years 1 , highlighting the pandemic potential of the CoV genus. While recently developed 48 antivirals show promise against MERS and SARS-CoV-2, further understanding of coronavirus 49 molecular virology is necessary to inform the design of more effective antiviral therapeutics and 50 vaccines 6, 7 . 51RNA structures in the ~30kb of single-stranded RNA 8 genomes of Coronavirus play 52 important roles in coronavirus replication 9, 5, 10, 11, 12, 13 . Given the length of coronavirus RNA 53 genomes, additional RNA structures likely exist that regulate CoV replication and disease 14 . In 54 this study, we used selective 2'-hydroxyl acylation by primer extension and mutational profiling 55 (SHAPE-MaP) 15 to identify highly stable, structured regions of the SARS-CoV, MERS-CoV, and 56 SARS-CoV-2 genomes. Our results revealed novel areas of RNA structure across the genomes 57 of all three viruses. SHAPE-MaP analysis confirmed previously described structures, and also 58 revealed that SARS-like coronaviruses contain a greater number of highly structured RNA 59 regions than MERS-CoV. Comparing nucleotide variation across multiple strains of each virus, 60 we find that highly variable nucleotides rarely impact RNA secondary structure, suggesting the 61 existence of selective pressure against RNA secondary structure disruption. We also identified 62 dozens of conserved highly stable structured regions in SARS-CoV and SARS-CoV-2 that share...

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mentioning

confidence: 99%

Comparative analysis of coronavirus genomic RNA structure reveals conservation in SARS-like coronaviruses

Sanders

Fritch

Madden

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The surface glycoproteins of the SARS-CoV-2 are the primary target for vaccine development. One of the primary goals of human COVID-19 vaccines is to elicit a strong humoral immune response against the S protein [ 275 ]. Moreover, MERS-CoV-specific CD4+ and CD8+ T cells are detected in peripheral blood mononuclear cells (PBMC) in MERS-CoV-infected survivors [ 276 ].…”

Section: Treatments For Covid-19mentioning

confidence: 99%

Biomedical Science to Tackle the COVID-19 Pandemic: Current Status and Future Perspectives

et al. 2020

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The coronavirus infectious disease (COVID-19) pandemic emerged at the end of 2019, and was caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has resulted in an unprecedented health and economic crisis worldwide. One key aspect, compared to other recent pandemics, is the level of urgency, which has started a race for finding adequate answers. Solutions for efficient prevention approaches, rapid, reliable, and high throughput diagnostics, monitoring, and safe therapies are needed. Research across the world has been directed to fight against COVID-19. Biomedical science has been presented as a possible area for combating the SARS-CoV-2 virus due to the unique challenges raised by the pandemic, as reported by epidemiologists, immunologists, and medical doctors, including COVID-19’s survival, symptoms, protein surface composition, and infection mechanisms. While the current knowledge about the SARS-CoV-2 virus is still limited, various (old and new) biomedical approaches have been developed and tested. Here, we review the current status and future perspectives of biomedical science in the context of COVID-19, including nanotechnology, prevention through vaccine engineering, diagnostic, monitoring, and therapy. This review is aimed at discussing the current impact of biomedical science in healthcare for the management of COVID-19, as well as some challenges to be addressed.

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“…Developing treatment against SARS-CoV-2 will likely be useful for long-term protection, as it mutates slowly than the flu virus, so there is an urgent need for developing the vaccine. While live attenuated vaccines targeting respiratory viruses, including influenza viruses and adenoviruses, have been approved for use in humans, but these vaccines have the chance to revert back to the virulent strain [56] or recombination with parental/other strains [57] . Elaine et al, have shown the efficacy of live attenuated strain lacking E-gene against SARS-CoV-1 infections in syrian golden hamsters [58] .…”

Section: Management and Treatment Optionsmentioning

confidence: 99%

Insights of Novel Coronavirus (SARS-CoV-2) disease outbreak, management and treatment

Kumar¹,

Batra²,

Malik

2020

AIMS Microbiology

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Emerging and re-emerging viral diseases poses a threat to living organisms, and led to serious concern to humankind and public health. The last two decades, viral epidemics such as the severe acute respiratory syndrome (SARS-CoV) reported in the years 2002–2003, and H1N1 influenza (Swine flu) in 2009, middle east respiratory syndrome (MERS-CoV) from Saudi Arabia in 2012, Ebola virus in 2014–2016, and Zika virus in 2015. The recent outbreak of 2019-CoV-2 or severe acute respiratory syndrome-2 (SARS-CoV-2), novel coronavirus (2019-nCoV, or 2019 disease, COVID-19) in Dec 2019, from, Wuhan city of China, has severe implications of health concerns to the whole world, due to global spread and high health risk. More than 423349 deaths had occurred globally and is still increasing every day. The whole world is under a health emergency, and people are advised to stay at their homes to avoid the spread of person-to-person infection, and advised to maintain social distancing. The advancement in clinical diagnosis techniques like Real-Time PCR (RT-PCR), immunological, microscopy, and geographic information system (GIS) mapping technology helped in tacking the rapid diagnosis and tracking viral infection in a short period. In the same way, artificial intelligence (AI), combinatorial chemistry, and deep learning approaches help to find novel therapeutics in less time and wide applicability in biomedical research. National Institute of Allergy and Infectious Diseases (NIAID) has started the clinical trials of investigation COVID-19 vaccine. Therefore, we can expect vaccines to be available for this deadly disease in the coming few months.

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The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses

Cited by 100 publications

References 348 publications

Comparative analysis of coronavirus genomic RNA structure reveals conservation in SARS-like coronaviruses

Comparative analysis of coronavirus genomic RNA structure reveals conservation in SARS-like coronaviruses

Biomedical Science to Tackle the COVID-19 Pandemic: Current Status and Future Perspectives

Insights of Novel Coronavirus (SARS-CoV-2) disease outbreak, management and treatment

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