Combating COVID-19 and its co-infection by Aspergillus tamarii SP73-EGY using in vitro and in silico Studies

Sci Rep. 2025 Jan 3;15(1):685. doi: 10.1038/s41598-024-77854-0.

Abstract

The COVID-19 pandemic has caused significant mortality and morbidity for millions of people. Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) virus is capable of causing severe and fatal diseases. We evaluated the antiviral properties of Aspergillus tamarii SP73-EGY isolate extract against low pathogenic coronavirus (229E), Adeno-7- and Herpes-2 viruses. The extract showed a high selectivity index (SI = 43.4) and a significant inhibition of 229E (IC50 = 8.205 μg/ml). It was stronger than the drug control, remdesivir (IC50 = 38.2 μg/ml, SI = 7.29). However, the extract showed minimal efficacy against Adeno-7- and Herpes-2-Viruses (IC50 = 22.52, 47.79 μg/ml, and SI = 6.75, 5.08, respectively). It exhibited profound efficacy against the highly pathogenic SARS-CoV-2 (IC50 = 8.306 μg/ml, SI = 42.2). Kojic acid, the primary component of the extract, showed substantial antiviral activity against SARS-CoV-2 (IC50 = 23.4 μg/ml, SI = 5.6), Remdesivir (IC50 = 4.55 μg/ml, SI = 61.45). Therefore, the extract demonstrated the most notable antiviral characteristics against coronavirus infection. Co-infecting microorganisms may contribute to immune system deterioration and airway injury caused by SARS-CoV-2. The extract showed significant efficacy against E. coli and P. aeruginosa, with an inhibition range of 3.5-10 mm at a concentration of 200 mg/ml. A molecular docking study showed that hexadecanoic, Kojic, octanoic acids, and 4(4-Methylbenzylidene)cyclohexane-1,3-dione have stronger binding affinity to the SARS-CoV-2 Mpro than Remdesivir. Molecular dynamics simulations were employed to examine the structural stability and flexibility of these complexes. This confirmed the high binding affinities of Kojic acid and 4(4-Methylbenzylidene)cyclohexane-1,3-dione, thereby proving their potential as novel anti-SARS-CoV-2.

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Adenosine Monophosphate / therapeutic use
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Alanine / therapeutic use
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • Aspergillus*
  • COVID-19 Drug Treatment*
  • COVID-19* / virology
  • Coinfection* / microbiology
  • Coinfection* / virology
  • Computer Simulation
  • Humans
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation
  • SARS-CoV-2* / drug effects

Substances

  • Antiviral Agents
  • remdesivir
  • Adenosine Monophosphate
  • Alanine