Current Situation in Chemoprophylaxis and Therapeutic Treatment of Covid-19

Bosilkovski, Mile; Jakimovski, Dejan; Poposki, Kostadin; Mateska, Sofija; Grujoski, Milan; Dimzova, Marija

doi:10.53582/amj2221004b

Cited by 1 publication

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various treatment strategies have emerged with the appearance of COVID-19, including conventional drug-based approaches, peptides, , sulfonated glyco-dendrimers, monoclonal antibodies, plasma therapy, and mechanical ventilation . Among drug-based treatment strategies, the nucleoside analog prodrug Remdesivir (GS-5734) has received much attention due to its remarkable antiviral effect for SARS-CoV-1 and MERS-CoV in preclinical trials and animal studies. , However, recent clinical results obtained from a large cohort of 330 patients in 30 different countries suggest that the drug appears to have no significant effect on COVID-19 mortality, contradicting previous findings . Alternatively, oral antiviral drugs such as Paxlovid (nirmatrelvir/ritonavir) and Molnupiravir (Lagevrio) have been authorized for preventing mild to moderate COVID-19 from worsening.…”

Section: Introductionmentioning

confidence: 99%

“…Alternatively, oral antiviral drugs such as Paxlovid (nirmatrelvir/ritonavir) and Molnupiravir (Lagevrio) have been authorized for preventing mild to moderate COVID-19 from worsening. However, these oral medications interact badly with other concurrent medications which have the potential to cause serious adverse effects, such as impaired taste and high blood pressure …”

Section: Introductionmentioning

confidence: 99%

“… 17 , 18 However, recent clinical results obtained from a large cohort of 330 patients in 30 different countries suggest that the drug appears to have no significant effect on COVID-19 mortality, contradicting previous findings. 19 Alternatively, oral antiviral drugs such as Paxlovid (nirmatrelvir/ritonavir) and Molnupiravir (Lagevrio) have been authorized for preventing mild to moderate COVID-19 from worsening. However, these oral medications interact badly with other concurrent medications which have the potential to cause serious adverse effects, such as impaired taste and high blood pressure.…”

Section: Introductionmentioning

confidence: 99%

“…However, these oral medications interact badly with other concurrent medications which have the potential to cause serious adverse effects, such as impaired taste and high blood pressure. 19 …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dendrimer-Peptide Conjugates for Effective Blockade of the Interactions between SARS-CoV-2 Spike Protein and Human ACE2 Receptor

Jeong

Mickel

et al. 2022

Biomacromolecules

View full text Add to dashboard Cite

The coronavirus disease 2019 (COVID-19) pandemic has threatened the stability of global healthcare, which is becoming an endemic issue. Despite the development of various treatment strategies to fight COVID-19, the currently available treatment options have shown varied efficacy. Herein, we have developed an avidity-based SARS-CoV-2 antagonist using dendrimer-peptide conjugates (DPCs) for effective COVID-19 treatment. Two different peptide fragments obtained from angiotensin-converting enzyme 2 (ACE2) were integrated into a single sequence, followed by the conjugation to poly(amidoamine) (PAMAM) dendrimers. We hypothesized that the strong multivalent binding avidity endowed by dendrimers would help peptides effectively block the interaction between SARS-CoV-2 and ACE2, and this antagonist effect would be dependent upon the generation (size) of the dendrimers. To assess this, binding kinetics of the DPCs prepared from generation 4 (G4) and G7 PAMAM dendrimers to spike protein of SARS-CoV-2 were quantitatively measured using surface plasmon resonance. The larger dendrimer-based DPCs exhibited significantly enhanced binding strength by 3 orders of magnitude compared to the free peptides, whereas the smaller one showed a 12.8-fold increase only. An in vitro assay using SARS-CoV-2-mimicking microbeads also showed the improved SARS-CoV-2 blockade efficiency of the G7-peptide conjugates compared to G4. In addition, the interaction between the DPCs and SARS-CoV-2 was analyzed using molecular dynamics (MD) simulation, providing an insight into how the dendrimer-mediated multivalent binding effect can enhance the SARS-CoV-2 blockade. Our findings demonstrate that the DPCs having strong binding to SARS-CoV-2 effectively block the interaction between ACE2 and SARS-CoV-2, providing a potential as a high-affinity drug delivery system to direct anti-COVID payloads to the virus.

show abstract