Since December 2019, coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in devastating consequences worldwide and infected more than 350,000 individuals and killed more than 16,000 people. SARS-CoV-2 is the seventh member of the coronavirus family to affect humans. Symptoms of COVID-19 include fever (88%), cough (68%), vomiting (5%) and diarrhoea (3.7%), and transmission of SARS-CoV-2 is thought to occur from human to human via respiratory secretions released by the infected individuals when coughing and sneezing. COVID-19 can be detected through computed tomography scans and confirmed through molecular diagnostics tools such as polymerase chain reaction. Currently, there are no effective treatments against SARS-CoV-2, hence antiviral drugs have been used to reduce the development of respiratory complications by reducing viral load. The purpose of this review is to provide a comprehensive update on the pathogenesis, clinical aspects, diagnosis, challenges and treatment of SARS-CoV-2 infections.
Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that cause infection of the central nervous system, granulomatous amoebic encephalitis (GAE) and primary amoebic meningoencephalitis (PAM), respectively. The fact that mortality rates for cases of GAE and PAM are more than 95% indicates the need for new therapeutic agents against those amoebae. Considering that curcumin exhibits a wide range of biological properties and has shown efficacy against Acanthamoeba castellanii, we evaluated the amoebicidal properties of curcumin against N. fowleri and B. mandrillaris. Curcumin showed significant amoebicidal activities with an AC 50 of 172 and 74 μM against B. mandrillaris and N. fowleri, respectively. Moreover, these compounds were also conjugated with gold nanoparticles to further increase their amoebicidal activities. After conjugation with gold nanoparticles, amoebicidal activities of the drugs were increased by up to 56 and 37% against B. mandrillaris and N. fowleri, respectively. These findings are remarkable and suggest that clinically available curcumin and our gold-conjugated curcumin nanoparticles hold promise in the improved treatment of fatal infections caused by brain-eating amoebae and should serve as a model in the rationale development of therapeutic interventions against other infections.
Brain-eating
amoebae cause devastating infections in the central
nervous system of humans, resulting in a mortality rate of 95%. There
are limited effective therapeutic options available clinically for
treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis
caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz
conjugated to gold and silver nanoparticles has significant antiamoebic
activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles
were synthesized by the one-phase reduction method and were characterized
by ultraviolet–visible spectrophotometry and atomic force microscopy.
Both metals were facilely stabilized by the coating of guanabenz,
which was examined by surface plasmon resonance determination. The
average size of gold nanoconjugated guanabenz was found to be 60 nm,
whereas silver nanoparticles were produced in a larger size distribution
with the average diameter of around 100 nm. Guanabenz and its noble
metal nanoconjugates exhibited potent antiamoebic effects in the range
of 2.5 to 100 μM against both amoebae. Nanoparticle conjugation
enhanced the antiamoebic effects of guanabenz, as more potent activity
was observed at a lower effective concentration (2.5 and 5 μM)
compared to the drug alone. Moreover, encystation and excystation
assays revealed that guanabenz inhibits the interconversion between
the trophozoite and cyst forms of A. castellanii. Cysticdal effects against N. fowleri were
also observed. Notably, pretreatment of A. castellanii with guanabenz and its nanoconjugates exhibited a significant reduction
in the host cell cytopathogenicity from 65% to 38% and 2% in case
of gold and silver nanoconjugates, respectively. Moreover, the cytotoxic
evaluation of guanabenz and its nanoconjugates revealed negligible
cytotoxicity against human cells. Guanabenz is already approved for
hypertension and crosses the blood–brain barrier; the results
of our current study suggest that guanabenz and its conjugated gold
and silver nanoparticles can be repurposed as a potential drug for
treating brain-eating amoebic infections.
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