SARS-CoV-2: vaccines in the pandemic era

Li, Dandan; Li, Qihan

doi:10.1186/s40779-020-00296-y

Cited by 53 publications

(53 citation statements)

References 93 publications

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“… 2 The vaccines have been developed at an amazing pace, and vaccination has already started in several countries. 3 However, only one small-molecule drug, remdesivir, 4 , 5 a broad-spectrum RNA-dependent RNA polymerase inhibitor, 6 − 8 is currently fully approved for treatment of COVID-19, but small-molecule drugs are urgently needed for people who, for various reasons, cannot be vaccinated or become sick before or despite vaccination. SARS-CoV-2 and other coronaviruses have an unusually large genome (∼30 000 bp) for single-stranded positive-sense RNA viruses.…”

mentioning

confidence: 99%

The Structure-Based Design of SARS-CoV-2 nsp14 Methyltransferase Ligands Yields Nanomolar Inhibitors

Otava

Šála

et al. 2021

ACS Infect. Dis.

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COVID-19, caused by the SARS-CoV-2 virus, is responsible for a global pandemic that has paralyzed the normal life in many countries around the globe. Therefore, the preparation of both effective vaccines and potential therapeutics has become a major research priority in the biotechnology sector. Both viral proteins and selected host factors are important targets for the treatment of this disease. Suitable targets for antiviral therapy include i.a. viral methyltransferases, which allow the viral mRNA to be efficiently translated and protect the viral RNA from the innate immune system. In this study, we have focused on the structure-based design of the inhibitors of one of the two SARS-CoV-2 methyltransferases, nsp14. This methyltransferase catalyzes the transfer of the methyl group from S-adenosyl-L-methionine (SAM) to cap the guanosine triphosphate moiety of the newly synthesized viral RNA, yielding the methylated capped RNA and S-adenosyl-L-homocysteine (SAH). The crystal structure of SARS-CoV-2 nsp14 is unknown; we have taken advantage of its high homology to SARS-CoV nsp14 and prepared its homology model, which has allowed us to identify novel SAH derivatives modified at the adenine nucleobase as inhibitors of this important viral target.We have synthesized and tested the designed compounds in vitro and shown that these derivatives exert unprecedented inhibitory activity against this crucial enzyme. The docking studies nicely explain the contribution of an aromatic part attached by a linker to the position 7 of the 7-deaza analogues of SAH. Our results will serve as an important source of information for the subsequent development of new antivirals to combat COVID-19. File list (2) download file view on ChemRxiv nsp14_chemRxiv_Tomas.pdf (1.29 MiB) download file view on ChemRxiv chemRxiv_Supporting_final.pdf (4.16 MiB) The structure-based design of SARS-CoV-2 nsp14 methyltransferase ligands yields nanomolar

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mentioning

confidence: 99%

The Structure-Based Design of SARS-CoV-2 nsp14 Methyltransferase Ligands Yields Nanomolar Inhibitors

Otava

Šála

et al. 2021

ACS Infect. Dis.

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“…Other vaccines are being produced using classical methods either via the inactivation or attenuation of the wild-type virus, such as BBIBP-CorV developed by the Beijing Institute of Biological Products and CoronaVac by Sinovac. 66 …”

Section: Pathophysiology Of Disease and Clinical Managementmentioning

confidence: 99%

Understanding the Molecular Biology of SARS-CoV-2 and the COVID-19 Pandemic: A Review

Alsobaie¹

2021

IDR

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Coronaviruses are named after the crown-like spike proteins on their surface. In the 21st century, three coronaviruses, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome related coronavirus (MERS-CoV), have emerged in the human population, presumably evolving from pathogens infecting other animals. Coronaviruses are enveloped viruses responsible for 15–30% of the atypical pneumonia cases in humans worldwide. The current coronavirus disease 2019 (COVID-19) pandemic is caused by the newest SARS virus, SARS-CoV-2, an enveloped, positive-sense, single-stranded RNA betacoronavirus of the family Coronaviridae. As of April 2021, the World Health Organization has reported more than 3 million deaths from COVID-19 and more than 140 million people have been infected with the virus, thereby making it the worst SARS pandemic of all time. Here, I review the current understanding of the molecular biology of coronaviruses and their host interactions, bringing together knowledge of the infection process to aid in the development of therapeutic drugs and/or vaccines against SARS-CoV-2. I also briefly overview the current situation of available treatments, vaccinations, and emerging strains.

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“…COVID-19 symptoms range from pneumonia to severe lung, heart, liver, kidney, neurological or gastrointestinal dysfunction [ 2 ]. While great efforts have been employed to provide effective SARS-CoV-2 vaccines [ 3 , 4 ], their success is overshadowed by the emergence of viral escape mutants and the shortcomings in developing targeted antiviral treatments. A meta-analysis by [ 5 ] demonstrates that in non-severe cases of COVID-19, there is little to no evidence for effective use of ribavirin, hydroxychloroquine, umifenovir, lopinavir/ritonavir, or interferon [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…While antiviral medication development was less fruitful, as of March 2021, there are 13 vaccines for SARS-CoV-2 in use, most of them targeting the spike (S) protein [ 3 , 8 ]. Albeit the successes in vaccine development, reports of mutations are increasing.…”

Section: Introductionmentioning

confidence: 99%

Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms Guanylate Kinase as Robust Potential Antiviral Target

Renz

Widerspick

Dräger

2021

Genes

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The current SARS-CoV-2 pandemic is still threatening humankind. Despite first successes in vaccine development and approval, no antiviral treatment is available for COVID-19 patients. The success is further tarnished by the emergence and spreading of mutation variants of SARS-CoV-2, for which some vaccines have lower efficacy. This highlights the urgent need for antiviral therapies even more. This article describes how the genome-scale metabolic model (GEM) of the host-virus interaction of human alveolar macrophages and SARS-CoV-2 was refined by incorporating the latest information about the virus’s structural proteins and the mutant variants B.1.1.7, B.1.351, B.1.28, B.1.427/B.1.429, and B.1.617. We confirmed the initially identified guanylate kinase as a potential antiviral target with this refined model and identified further potential targets from the purine and pyrimidine metabolism. The model was further extended by incorporating the virus’ lipid requirements. This opened new perspectives for potential antiviral targets in the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play a pivotal role in viral replication. The guanylate kinase is even a robust target in all investigated mutation variants currently spreading worldwide. These new insights can guide laboratory experiments for the validation of identified potential antiviral targets. Only the combination of vaccines and antiviral therapies will effectively defeat this ongoing pandemic.

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SARS-CoV-2: vaccines in the pandemic era

Cited by 53 publications

References 93 publications

The Structure-Based Design of SARS-CoV-2 nsp14 Methyltransferase Ligands Yields Nanomolar Inhibitors

The Structure-Based Design of SARS-CoV-2 nsp14 Methyltransferase Ligands Yields Nanomolar Inhibitors

Understanding the Molecular Biology of SARS-CoV-2 and the COVID-19 Pandemic: A Review

Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms Guanylate Kinase as Robust Potential Antiviral Target

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