A Photoactivable Natural Product with Broad Antiviral Activity against Enveloped Viruses, Including Highly Pathogenic Coronaviruses

Abstract

The SARS-CoV-2 outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against HCoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and MERS-CoV, and its mechanism of action was further assessed, showing that Pba is an inhibitor of coronavirus entry by directly targeting the viral particle. Interestingly, the antiviral activity of Pba depends on light exposure, and Pba was shown to inhibit virus-cell fusion by stiffening the viral membrane as demonstrated by cryo-electron microscopy. Moreover, Pba was shown to be broadly active against several other enveloped viruses, and reduced SARS-CoV-2 and MERS-CoV replication in primary human bronchial epithelial cells. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity that holds potential for COVID-19 therapy or disinfection of SARS-CoV-2 contaminated surfaces.

The Photosensitizer Temoporfin (mTHPC) – Chemical, Pre‐clinical and Clinical Developments in the Last Decade†‡

“…In a natural product screening study pheophorbide a (a chlorophyll derivative) showed a light‐dependent antiviral activity on SARS‐CoV‐2 and inhibited virus‐cell fusion. A similar mechanism was shown for temoporfin; however, it exhibited only moderate antiviral activity (582). Note, temoporfin has also been suggested in a pre‐print as a potential blocker of SARS‐CoV‐2 E channel based on a docking study (583).…”

Tratamento adjuvante no câncer superficial de bexiga

“…As células tumorais crescem mais rápido e, portanto, absorvem mais substâncias do ambiente externo, o que pode ajudar a aumentar a concentração intracelular do Fs [67]. Em 1912, Meyer-Betz demonstrou que a (HpD), é um composto isolado da hemoglobina, era um Fs muito poderoso com propriedades de localização tumoral [71,72].…”

O apoio institucional como estratégia para a implantação da política nacional de saúde integral da população negra no Rio Grande do Sul

“…Em 1912, Meyer-Betz demonstrou que a (HpD), é um composto isolado da hemoglobina, era um Fs muito poderoso com propriedades de localização tumoral [71,72].…”