Role of Flavonoids against COVID-19

The novel coronavirus disease (COVID-19) has entered a threatening stage all over the world. Many lives have been lost, and many more are in need of treatment. The mild symptoms may include fever and dry cough, but in severe cases, it could lead to pneumonia and ultimately death in some instances. Though medical scientists all over the globe are working hard to develop a treatment for this disease, yet no definite cure has been found. To date, the treatment strategy is based on adopting strategies to break the transmission of the virus and repurposing of the old drugs to prevent the loss of life. Among the various potent candidates, flavonoids may play a protective role in these times. Studies have already proven various health-promoting properties of flavonoids in earlier viral diseases, like SARS and MERS. Since ancient times, been plants have used to treat a number of human diseases. Different phytoproducts have been previously described to inhibit the replication of numerous viruses. Despite the positive reports for plant-based medications, no successful clinical trials on phytoproducts as anti-COVID agents have been conducted to date. This review highlights the efficacy of flavonoids as a treatment strategy either alone or in combination with other drugs.

Allogenous Selection of Mutational Collateral Resistance: Old Drugs Select for New Resistance Within Antibiotic Families

Allogeneous selection occurs when an antibiotic selects for resistance to more advanced members of the same family. The mechanisms of allogenous selection are (a) collateral expansion, when the antibiotic expands the gene and gene-containing bacterial populations favoring the emergence of other mutations, inactivating the more advanced antibiotics; (b) collateral selection, when the old antibiotic selects its own resistance but also resistance to more modern drugs; (c) collateral hyper-resistance, when resistance to the old antibiotic selects in higher degree for populations resistant to other antibiotics of the family than to itself; and (d) collateral evolution, when the simultaneous or sequential use of antibiotics of the same family selects for new mutational combinations with novel phenotypes in this family, generally with higher activity (higher inactivation of the antibiotic substrates) or broader spectrum (more antibiotics of the family are inactivated). Note that in some cases, collateral selection derives from collateral evolution. In this article, examples of allogenous selection are provided for the major families of antibiotics. Improvements in minimal inhibitory concentrations with the newest drugs do not necessarily exclude “old” antibiotics of the same family of retaining some selective power for resistance to the newest agents. If this were true, the use of older members of the same drug family would facilitate the emergence of mutational resistance to the younger drugs of the family, which is frequently based on previously established resistance traits. The extensive use of old drugs (particularly in low-income countries and in farming) might be significant for the emergence and selection of resistance to the novel members of the family, becoming a growing source of variation and selection of resistance to the whole family. In terms of future research, it could be advisable to focus antimicrobial drug discovery more on the identification of new targets and new (unique) classes of antimicrobial agents, than on the perpetual chemical exploitation of classic existing ones.

In Drug Repurposing Tactics Against Covid-19

Background: Now a days, due to high substantial costs and slow rate of new drug discovery and development, repurposing of old drugs to treat diseases is becoming an emerging drug approach. Repurposing approach involves the identification of new pharmacological activity for old drugs. This strategy is time saving, more effective and has lesser failure risks. Methods: The present review involves the challenge by summarising the COVID‐19 drug repurposing research into three large groups, including repurposing of Antivirals, Anti-Cancer Drugs, existing Quinoline based drugs. Results: Number of medications, for example remdesivir, umifenovir, favipiravin, ribavirin, rapamycin, carfilzomib, chloroquine and hydroxychloroquine, saquinavir, elvitegravir, and oxolinic acid and rilapladib have indicated inhibitory effects against the SARS-CoV2 in vitro just as in clinical conditions. These medications either act through infection related targets, for example, RNA genome, polypeptide pressing and take-up pathways or target have related pathways including angiotensin-changing over protein 2 (ACE2) receptors also, inflammatory pathways. Conclusion: From the literature studies it can be concluded that, In the current scenario repositioning of the drugs could be considered the new avenue for the treatment of COVID-19.

The acid sphingomyelinase/ceramide system in COVID-19

Acid sphingomyelinase (ASM) cleaves sphingomyelin into the highly lipophilic ceramide, which forms large gel-like rafts/platforms in the plasma membrane. We showed that SARS-CoV-2 uses these platforms for cell entry. Lowering the amount of ceramide or ceramide blockade due to inhibitors of ASM, genetic downregulation of ASM, anti-ceramide antibodies or degradation by neutral ceramidase protected against infection with SARS-CoV-2. The addition of ceramide restored infection with SARS-CoV-2. Many clinically approved medications functionally inhibit ASM and are called FIASMAs (functional inhibitors of acid sphingomyelinase). The FIASMA fluvoxamine showed beneficial effects on COVID-19 in a randomized prospective study and a prospective open-label real-world study. Retrospective and observational studies showed favorable effects of FIASMA antidepressants including fluoxetine, and the FIASMA hydroxyzine on the course of COVID-19. The ASM/ceramide system provides a framework for a better understanding of the infection of cells by SARS-CoV-2 and the clinical, antiviral, and anti-inflammatory effects of functional inhibitors of ASM. This framework also supports the development of new drugs or the repurposing of “old” drugs against COVID-19.

Iso-Partricin, an Aromatic Analogue of Amphotericin B: How Shining Light on Old Drugs Might Help Create New Ones

Partricin is a heptaene macrolide antibiotic complex that exhibits exceptional antifungal activity, yet poor selective toxicity, in the pathogen/host system. It consists of two compounds, namely partricin A and B, and both of these molecules incorporate two cis-type bonds within their heptaenic chromophores: 28Z and 30Z. In this contribution, we have proven that partricins are susceptible to a chromophore-straightening photoisomerization process. The occurring 28Z→28E and 30Z→30E switches are irreversible in given conditions, and they are the only structural changes observed during the experiment. The obtained all-trans partricin’s derivatives, namely iso-partricins A and B, exhibit very promising features, potentially resulting in the improvement of their selective toxicity.

Allogenous Selection of Mutational Collateral Resistance: Old Drugs Select for New Resistances Within Antibiotic Families

Allogeneous selection occurs when an antibiotic selects for resistance to more advanced members of the same family. The mechanisms of allogenous selection are (a) collateral expansion, when the antibiotic expands the gene and gene-containing bacterial populations favoring the emergence of other mutations, inactivating the more advanced antibiotics; (b) collateral selection, when the old antibiotic selects its own resistance but also resistances to more modern drugs; (c) collateral hyper-resistance, when resistance to the old antibiotic selects in higher degree for populations resistant to other antibiotics of the family than to itself; and (d) collateral evolution, when the simultaneous or sequential use of antibiotics of the same family selects for new mutational combinations with novel phenotypes, generally with higher activity or broader spectrum. Note that in some cases, collateral selection derives from collateral evolution. In this study, examples of allogenous selection are provided for the major families of antibiotics. Improvements in minimal inhibitory concentrations with the newest drugs do not necessarily exclude “old” antibiotics of the same family of retaining some selective power for resistance to the newest agents. If this were true, the use of older members of the same drug family would facilitate the emergence of mutational resistance to the younger drugs of the family, which is frequently based on previously established resistance traits. The extensive use of old drugs (particularly in low-income countries and in farming) might be significant for the emergence and selection of resistances to the novel members of the family, becoming a growing source of variation and selection of resistance to the whole family. In terms of future research, it could be advisable to focus antimicrobial drug discovery more on the identification of new targets and new (unique) classes of antimicrobial agents, than on the perpetual chemical exploitation of classic existing ones.