Coronavirus Pandemic—Therapy and Vaccines

Lundström, Kenneth

doi:10.3390/biomedicines8050109

Cited by 50 publications

(71 citation statements)

References 180 publications

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“…SARS-CoV-2, a member of the Betacoronavirus genus, is an enveloped positive-sense, RNA virus responsible for a current pandemic 1 . Because of its profound impact on society and human health there is an urgent need to understand SARS-CoV-2 replication requirements and to identify therapeutic strategies 2 .…”

Section: Introductionmentioning

confidence: 99%

Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication

Silvas

Jureka

Nicolini

et al. 2020

Preprint

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Therapeutics targeting replication of SARS coronavirus 2 (SARS-CoV-2) are urgently needed. Coronaviruses rely on host membranes for entry, establishment of replication centers and egress. Compounds targeting cellular membrane biology and lipid biosynthetic pathways have previously shown promise as antivirals and are actively being pursued as treatments for other conditions. Here, we tested small molecule inhibitors that target membrane dynamics or lipid metabolism. Included were inhibitors of the PI3 kinase VPS34, which functions in autophagy, endocytosis and other processes; Orlistat, an inhibitor of lipases and fatty acid synthetase, is approved by the FDA as a treatment for obesity; and Triacsin C which inhibits long chain fatty acyl-CoA synthetases. VPS34 inhibitors, Orlistat and Triacsin C inhibited virus growth in Vero E6 cells and in the human airway epithelial cell line Calu-3, acting at a post-entry step in the virus replication cycle. Of these the VPS34 inhibitors exhibit the most potent activity.

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Section: Introductionmentioning

confidence: 99%

Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication

Silvas

Jureka

Nicolini

et al. 2020

Preprint

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“…The genome of SARS-CoV-2 encodes for the structural proteins spike (S), envelope (E), membrane (M) and nucleocapsid (N) as well as a number of accessory and non-structural proteins ( Figure 1 ) ( 13 ). The M and N proteins give the virion its shape, and the S proteins appear as spikes on the viral surface giving it a solar corona appearance.…”

Section: Sars-cov-2 Structure and Functionmentioning

confidence: 99%

“…While subunit vaccines are more focused on induction of humoral immunity, viral vector vaccines are able to induce robust cell mediated immunity (CMI) in addition to Abs and have been shown in animal models to protect against challenge with pathogenic coronaviruses ( 51 ). A modified vaccinia Ankara (MVA) vector expressing a MERS-CoV recombinant protein induced T cell responses and nAbs in mice, while a rabies virus-based SARS-CoV-1 vaccine protected mice against SARS-CoV-1 challenge ( 13 ).…”

Section: Different Vaccine Approaches Used In Covid-19 Vaccine Develomentioning

confidence: 99%

“…A series of animal studies with SARS-CoV-1 nucleic acid-based vaccines have shown induction of nAbs and cellular immunity, with partial protection against turkey CoV challenge ( 13 ) and vaccine-induced Ab-mediated protection to the S protein in mice ( 51 ). Twelve DNA-based SARS-CoV-2 vaccines are currently in preclinical development and 4 more have entered phase 1/2 clinical trials ( Table 1 ).…”

Section: Different Vaccine Approaches Used In Covid-19 Vaccine Develomentioning

confidence: 99%

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Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines

et al. 2020

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There are currently around 200 SARS-CoV-2 candidate vaccines in preclinical and clinical trials throughout the world. The various candidates employ a range of vaccine strategies including some novel approaches. Currently, the goal is to prove that they are safe and immunogenic in humans (phase 1/2 studies) with several now advancing into phase 2 and 3 trials to demonstrate efficacy and gather comprehensive data on safety. It is highly likely that many vaccines will be shown to stimulate antibody and T cell responses in healthy individuals and have an acceptable safety profile, but the key will be to confirm that they protect against COVID-19. There is much hope that SARS-CoV-2 vaccines will be rolled out to the entire world to contain the pandemic and avert its most damaging impacts. However, in all likelihood this will initially require a targeted approach toward key vulnerable groups. Collaborative efforts are underway to ensure manufacturing can occur at the unprecedented scale and speed required to immunize billions of people. Ensuring deployment also occurs equitably across the globe will be critical. Careful evaluation and ongoing surveillance for safety will be required to address theoretical concerns regarding immune enhancement seen in previous contexts. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. We provide details of some of the frontrunner vaccines and discuss potential issues including adverse effects, scale-up and delivery.

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“…COVID-19 vaccine development includes: (i) inactivated or live attenuated virus, (ii) subunit vaccines, which use part of the virus to mount an immune response, (iii) genetic vaccines (delivering messenger RNA to cells to counteract the virus RNA), (iv) viral vector vaccines engineered to produce part of the viral protein to mount an immune response, and (v) targeting the viral reproductive machinery [ 84 , 85 ].…”

Section: Current Strategies For the Prevention And Treatment Of Comentioning

confidence: 99%

Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19

McGowan

Haddadi

Nassif

et al. 2020

IJMS

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The world is currently experiencing the worst health pandemic since the Spanish flu in 1918—the COVID-19 pandemic—caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the world’s third wake-up call this century. In 2003 and 2012, the world experienced two major coronavirus outbreaks, SARS-CoV-1 and Middle East Respiratory syndrome coronavirus (MERS-CoV), causing major respiratory tract infections. At present, there is neither a vaccine nor a cure for COVID-19. The severe COVID-19 symptoms of hyperinflammation, catastrophic damage to the vascular endothelium, thrombotic complications, septic shock, brain damage, acute disseminated encephalomyelitis (ADEM), and acute neurological and psychiatric complications are unprecedented. Many COVID-19 deaths result from the aftermath of hyperinflammatory complications, also referred to as the “cytokine storm syndrome”, endotheliitus and blood clotting, all with the potential to cause multiorgan dysfunction. The sphingolipid rheostat plays integral roles in viral replication, activation/modulation of the immune response, and importantly in maintaining vasculature integrity, with sphingosine 1 phosphate (S1P) and its cognate receptors (SIPRs: G-protein-coupled receptors) being key factors in vascular protection against endotheliitus. Hence, modulation of sphingosine kinase (SphK), S1P, and the S1P receptor pathway may provide significant beneficial effects towards counteracting the life-threatening, acute, and chronic complications associated with SARS-CoV-2 infection. This review provides a comprehensive overview of SARS-CoV-2 infection and disease, prospective vaccines, and current treatments. We then discuss the evidence supporting the targeting of SphK/S1P and S1P receptors in the repertoire of COVID-19 therapies to control viral replication and alleviate the known and emerging acute and chronic symptoms of COVID-19. Three clinical trials using FDA-approved sphingolipid-based drugs being repurposed and evaluated to help in alleviating COVID-19 symptoms are discussed.

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Coronavirus Pandemic—Therapy and Vaccines

Cited by 50 publications

References 180 publications

Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication

Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication

Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines

Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19

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