62 Is ribavirin antiviral effect in humans mediated by mutagenic properties resulting in error catastrophe?

On recation of cyclooctylamine with the sulfate of S-methylisothiourea cyclooctylguanidine was formed which was acylated with the methyl esters of 5-halogeno- and 3,5-dihalogeno-2-alkoxybenzoic acids. The 1-acyl-3-cyclooctylguanidine I-XVII formed were tested for their antiviral effect against the influenza virus A/NWS, A-PR8 and A2 Singapore, and further against the viruses NDV, herpes 2, vaccinia and WEE. In the in vivo test against the influenza virus A2 Singapore and herpes simplex 1-(5-bromo-2-dodecyloxybenzoyl)-3-cyclooctylguanidine is more active and less toxic than cyclooctylamine and 1-cyclooctylguanidine.

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Immunological Aspects Related to Viral Infections in Severe Asthma and the Role of Omalizumab

Biomedicines ◽

10.3390/biomedicines9040348 ◽

2021 ◽

Vol 9 (4) ◽

pp. 348

Author(s):

Francesco Menzella ◽

Giulia Ghidoni ◽

Carla Galeone ◽

Silvia Capobelli ◽

Chiara Scelfo ◽

...

Keyword(s):

Innate Immunity ◽

Severe Asthma ◽

Viral Infections ◽

Respiratory Infections ◽

Antiviral Effect ◽

Point Of View ◽

Type I ◽

Effector Cells ◽

Viral Spread ◽

Increased Risk

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although extremely limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which can stabilize the effector cells, and is becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allow a great improvement in the management of asthma.

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Saturation of DNA Mismatch Repair and Error Catastrophe by a Base Analogue in Escherichia coli

Genetics ◽

10.1093/genetics/161.4.1363 ◽

2002 ◽

Vol 161 (4) ◽

pp. 1363-1371

Author(s):

Kazuo Negishi ◽

David Loakes ◽

Roel M Schaaper

Keyword(s):

Escherichia Coli ◽

Mismatch Repair ◽

Dna Mismatch Repair ◽

Repair System ◽

Mutagenic Action ◽

Wild Type ◽

Dna Mismatch ◽

Cell Counts ◽

Error Catastrophe ◽

Mismatch Repair System

Abstract Deoxyribosyl-dihydropyrimido[4,5-c][1,2]oxazin-7-one (dP) is a potent mutagenic deoxycytidine-derived base analogue capable of pairing with both A and G, thereby causing G · C → A · T and A · T → G · C transition mutations. We have found that the Escherichia coli DNA mismatch-repair system can protect cells against this mutagenic action. At a low dose, dP is much more mutagenic in mismatch-repair-defective mutH, mutL, and mutS strains than in a wild-type strain. At higher doses, the difference between the wild-type and the mutator strains becomes small, indicative of saturation of mismatch repair. Introduction of a plasmid containing the E. coli mutL+ gene significantly reduces dP-induced mutagenesis. Together, the results indicate that the mismatch-repair system can remove dP-induced replication errors, but that its capacity to remove dP-containing mismatches can readily be saturated. When cells are cultured at high dP concentration, mutant frequencies reach exceptionally high levels and viable cell counts are reduced. The observations are consistent with a hypothesis in which dP-induced cell killing and growth impairment result from excess mutations (error catastrophe), as previously observed spontaneously in proofreading-deficient mutD (dnaQ) strains.

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Antiviral Activity of the PropylamylatinTM Formula against the Novel Coronavirus SARS-CoV-2 In Vitro Using Direct Injection and Gas Assays in Virus Suspensions

Viruses ◽

10.3390/v13030415 ◽

2021 ◽

Vol 13 (3) ◽

pp. 415

Author(s):

Ashley N. Brown ◽

Gary Strobel ◽

Kaley C. Hanrahan ◽

Joe Sears

Keyword(s):

Propionic Acid ◽

Infectious Virus ◽

Direct Injection ◽

Plaque Assay ◽

Antiviral Effect ◽

Dependent Manner ◽

Global Public Health ◽

Novel Coronavirus ◽

The Individual

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of novel coronavirus disease 2019 (COVID-19), has become a severe threat to global public health. There are currently no antiviral therapies approved for the treatment or prevention of mild to moderate COVID-19 as remdesivir is only approved for severe COVID-19 cases. Here, we evaluated the antiviral potential of a Propylamylatin formula, which is a mixture of propionic acid and isoamyl hexanoates. The Propylamylatin formula was investigated in gaseous and liquid phases against 1 mL viral suspensions containing 105 PFU of SARS-CoV-2. Viral suspensions were sampled at various times post-exposure and infectious virus was quantified by plaque assay on Vero E6 cells. Propylamylatin formula vapors were effective at inactivating infectious SARS-CoV-2 to undetectable levels at room temperature and body temperature, but the decline in virus was substantially faster at the higher temperature (15 min versus 24 h). The direct injection of liquid Propylamylatin formula into viral suspensions also completely inactivated SARS-CoV-2 and the rapidity of inactivation occurred in an exposure dependent manner. The overall volume that resulted in 90% viral inactivation over the course of the direct injection experiment (EC90) was 4.28 µls. Further investigation revealed that the majority of the antiviral effect was attributed to the propionic acid which yielded an overall EC90 value of 11.50 µls whereas the isoamyl hexanoates provided at most a 10-fold reduction in infectious virus. The combination of propionic acid and isoamyl hexanoates was much more potent than the individual components alone, suggesting synergy between these components. These findings illustrate the therapeutic promise of the Propylamylatin formula as a potential treatment strategy for COVID-19 and future studies are warranted.

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