scholarly journals A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV

Viruses ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 448 ◽  
Author(s):  
Changfa Fan ◽  
Xi Wu ◽  
Qiang Liu ◽  
Qianqian Li ◽  
Susu Liu ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Respiratory Illness ◽  
Clinical Strain ◽  
Fusion Inhibitor ◽  
Dipeptidyl Peptidase 4 ◽  
Susceptibility To Infection ◽  
Inhibitor Peptide ◽  
Novel Model ◽  
Biosafety Level ◽  
Knockin Mouse

Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively.

scholarly journals Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 437
Author(s):  
Dean Gilham ◽  
Audrey L. Smith ◽  
Li Fu ◽  
Dalia Y. Moore ◽  
Abenaya Muralidharan ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Host Cells ◽  
Protein Inhibitor ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Surface Receptors ◽  
Bet Inhibitor ◽  
Epigenetic Machinery ◽  
Unexplored Area

Effective therapeutics are urgently needed to counter infection and improve outcomes for patients suffering from COVID-19 and to combat this pandemic. Manipulation of epigenetic machinery to influence viral infectivity of host cells is a relatively unexplored area. The bromodomain and extraterminal (BET) family of epigenetic readers have been reported to modulate SARS-CoV-2 infection. Herein, we demonstrate apabetalone, the most clinical advanced BET inhibitor, downregulates expression of cell surface receptors involved in SARS-CoV-2 entry, including angiotensin-converting enzyme 2 (ACE2) and dipeptidyl-peptidase 4 (DPP4 or CD26) in SARS-CoV-2 permissive cells. Moreover, we show that apabetalone inhibits SARS-CoV-2 infection in vitro to levels comparable to those of antiviral agents. Taken together, our study supports further evaluation of apabetalone to treat COVID-19, either alone or in combination with emerging therapeutics.

Half-life extension of the HIV-fusion inhibitor peptide TRI-1144 using a novel linker technology

2015 ◽  
Vol 93 ◽  
pp. 254-259 ◽  
Author(s):  
Eric L. Schneider ◽  
Gary W. Ashley ◽  
Lieve Dillen ◽  
Bart Stoops ◽  
Nigel E. Austin ◽  
...  
Keyword(s):  
Half Life ◽  
Life Extension ◽  
Fusion Inhibitor ◽  
Inhibitor Peptide

In situ depot formation of anti-HIV fusion-inhibitor peptide in recombinant protein polymer hydrogel

2017 ◽  
Vol 64 ◽  
pp. 116-125 ◽  
Author(s):  
Daisuke Asai ◽  
Taisei Kanamoto ◽  
Mitsuko Takenaga ◽  
Hideki Nakashima
Keyword(s):  
Recombinant Protein ◽  
Fusion Inhibitor ◽  
Polymer Hydrogel ◽  
Protein Polymer ◽  
Inhibitor Peptide ◽  
Anti Hiv

scholarly journals The effects of vitamin D on respiratory illnesses: a prospective natural treatment for COVID-19

2020 ◽  
Vol 3 (8) ◽  
pp. 124
Author(s):  
Danik Martirosyan ◽  
Charlotte Giordano
Keyword(s):  
Vitamin D ◽  
Clinical Trials ◽  
Treatment Option ◽  
Respiratory Illness ◽  
Vitamin D Supplementation ◽  
Respiratory Illnesses ◽  
Beneficial Effects ◽  
Additional Information ◽  
Susceptibility To Infection ◽  
Natural Treatment

Background: In the midst of COVID-19, healthcare specialists and researchers worldwide have been actively investigating treatments for this new disease. As of July 3rd, 2020, there have been a total of 11,048,509 confirmed cases in more than 188 countries and regions with more and more cases being identified every day. Though there have been a couple of medications given EUA status by the FDA such as chloroquine and hydroxychloroquine, remdesivir, and Fresenius Propoven, some of these treatments have been found to carry substantial health risks. Chloroquine and hydroxychloroquine, for example, were found to cause abnormal heart rhythms and facilitated higher rates of death among patients in clinical trials. For this reason, a more natural option such as vitamin D has the potential to be safer and more effective in the treatment of SARS-CoV-2 symptoms.Objective: In this study, I investigate the benefits of vitamin D supplementation as shown in previous clinical trials involving respiratory illnesses and discussed which foods are most rich in vitamin D. Ultimately, I aim to provide an understanding of the mechanisms by which vitamin D is acquired and the most effective amounts that people should regularly consume in order to strengthen their immune system.Methods: All of the case studies cited in this review were found through Google Scholar or NCBI by search queries such as “Vitamin D supplementation to treat respiratory illness.” Additional information regarding vaccinations and medications was sourced from the FDA and information about the nutritional value of foods was obtained from the USDA.Results: Vitamin D has been shown to have many beneficial effects on patients suffering from both respiratory and non-respiratory illnesses. These benefits include, but are not limited to, lowered susceptibility to infection and lower bacterial counts, reduced symptoms of illness, increased serum 25(OH)D, and corrected vitamin D deficiency.Conclusions: Given the striking symptomatic, molecular, and pathological similarities between infection from SARS-CoV-2 and other respiratory illnesses such as influenza, the positive results from vitamin D supplementation suggest that vitamin D may be a viable treatment option for SARS-CoV-2 symptoms. Through the consumption of vitamin D-rich foods like UV-exposed mushrooms, salmon, and trout, low serum 25(OH)D levels could be corrected and the reduction of symptoms could be naturally facilitated. Through the induction of cathelicidin and defensin, the regulation of cytokines, and the increased production of anti-microbial peptides, vitamin D has the potential to act as a natural treatment option without adverse side-effects like those caused by chloroquine and other proposed drugs.Keywords: Vitamin D; Deficiency; Respiratory Illness; COVID-19; Influenza; Cathelicidin; Defensin; SARS-CoV-2; ACE2; ANG II.

scholarly journals Antiviral and Immunomodulatory Effects of Phytochemicals from Honey against COVID-19: Potential Mechanisms of Action and Future Directions

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5017 ◽  
Author(s):  
Mohammad A. I. Al-Hatamleh ◽  
Ma’mon M. Hatmal ◽  
Kamran Sattar ◽  
Suhana Ahmad ◽  
Mohd Zulkifli Mustafa ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Potential Role ◽  
Antiviral Agents ◽  
Respiratory Illness ◽  
Mechanisms Of Action ◽  
Future Directions ◽  
Antiviral Effects ◽  
Global Pandemic ◽  
Phytochemical Components ◽  
Severe Respiratory Illness

The new coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has recently put the world under stress, resulting in a global pandemic. Currently, there are no approved treatments or vaccines, and this severe respiratory illness has cost many lives. Despite the established antimicrobial and immune-boosting potency described for honey, to date there is still a lack of evidence about its potential role amid COVID-19 outbreak. Based on the previously explored antiviral effects and phytochemical components of honey, we review here evidence for its role as a potentially effective natural product against COVID-19. Although some bioactive compounds in honey have shown potential antiviral effects (i.e., methylglyoxal, chrysin, caffeic acid, galangin and hesperidinin) or enhancing antiviral immune responses (i.e., levan and ascorbic acid), the mechanisms of action for these compounds are still ambiguous. To the best of our knowledge, this is the first work exclusively summarizing all these bioactive compounds with their probable mechanisms of action as antiviral agents, specifically against SARS-CoV-2.

Structure and conformation of HIV fusion inhibitor peptide T-1249 in presence of model membranes: A molecular dynamics study

2010 ◽  
Vol 946 (1-3) ◽  
pp. 119-124 ◽  
Author(s):  
A.M.T. Martins do Canto ◽  
A.J. Palace Carvalho ◽  
J.P. Prates Ramalho ◽  
Luís M.S. Loura
Keyword(s):  
Molecular Dynamics ◽  
Model Membranes ◽  
Fusion Inhibitor ◽  
Peptide T ◽  
Inhibitor Peptide

Repurposing fusion inhibitor peptide against SARS‐CoV ‐2

2021 ◽  
Author(s):  
Faiyaz Md. Efaz ◽  
Shafiqul Islam ◽  
Shafi Ahmad Talukder ◽  
Shaila Akter ◽  
Md. Zakaria Tashrif ◽  
...  
Keyword(s):  
Fusion Inhibitor ◽  
Inhibitor Peptide

There was a simultaneous outbreak of the zoonotic Nipah henipavirus in Wuhan - 4 out of 5 patients have the virus in Jinyintan Hospital , along with SARS-Cov2, in their metagenome - which seems to have resolved by itself

2020 ◽  
Author(s):  
Sandeep Chakraborty
Keyword(s):  
Viral Load ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Nipah Virus ◽  
Respiratory Illness ◽  
Lavage Fluid ◽  
Full Genome ◽  
The World ◽  
Severe Respiratory Illness ◽  
Biosafety Level

‘Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans’ [1] that orginates in bats [2]. It was first isolated in Malaysia and Singapore in 1999 - ‘late September 1998 and by mid-June 1999, more than 265 encephalitis cases, including 105 deaths, had been reported in Malaysia, and 11 cases of encephalitis or respiratory illness with one death had been reported in Singapore’ [3]. It keeps recurring in Bangladesh [4]. There was a 2018 outbreak in Kerala, India [5]. There seems to have been a simultaneous outbreak in Wuhan during Covid19 - which never got reported, and apparently resolved by itself.Metagenome from the bronchoalveolar lavage fluid of 5 Covid19 [6–8] patients from Wuhan (Accid:PRJNA605983) which showed very little SAR-Cov2 viral load (in the tens per million reads) in my analysis earlier [9].The metagenome also shows the co-infection with Nipah henipavirus virus in 4 out of 5 patients. The sequences are in SI:Nipah.fa - 167 reads in all.One can almost assemble the full genome (about 18kbps) from it. It seems to have originated from Bangladesh, though I have not done the phylogeny. Most reads are 100% identical, but some are (97% - 145/150).Maybe, we have looking for the wrong virus in the rest of the world - since Nipah is endemic to Southeast Asia, which seems to have been the least affected in Covid19.

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