Viral, host and environmental factors that favor anthropozoonotic spillover of coronaviruses: An opinionated review, focusing on SARS-CoV, MERS-CoV and SARS-CoV-2.

Environmental factors play a key role in the zoonotic transmission of emerging pathogenic viruses as mankind is constantly disturbing wildlife's ecosystems usually by cutting down forests to build human settlements or by catching wild animals for food, which deprives the viruses of their natural hosts and gives them opportunity to infect humans. In December 2019, a new coronavirus emerged from bats and was named SARS-CoV-2 by the International Committee for Taxonomy of Viruses, and the disease it causes named COVID-19 by the World Health Organization. Disease outbreaks such as SARS in 2002-2003, MERS in 2012 and the current COVID-19 pandemic are the result of higher mutation rates of coronaviruses and their unique capacity for genetic recombination, resulting in adaptations that make them more suitable to cross the species barriers and infect other species. This ability for host switching and interspecies infection is often attributed to the great diversity of these viruses, which is a result of viral and host factors such as the low fidelity of their RNA-dependent RNA polymerase, the high frequency of their homologous RNA recombination, and the adaptation of the S protein to bind host receptors like the angiotensin converting enzyme 2 (ACE2) in the case of SARS-CoV and SARS-CoV-2, and dipeptidyl peptidase 4 (DDP4) in MERS-CoV. This review presents an overview of the zoonotic transmission of SARS, MERS and COVID-19, focusing on the viral, host and environmental factors that favor the spillover of these viruses into humans, as well as the biological and ecological factors that make bats the perfect animal reservoir of infection for these viruses.

Synthesis of a natural chalcone and its prenyl analogs--evaluation of tumor cell growth-inhibitory activities, and effects on cell cycle and apoptosis.

Six prenyl (=3-methylbut-2-en-1-yl) chalcones (=1,3-diphenylprop-2-en-1-ones), 2-7, and one natural non-prenylated chalcone, 1, have been synthesized and evaluated for their in vitro growth-inhibitory activity against three human tumor cell lines. A pronounced dose-dependent growth-inhibitory effect was observed for all prenylated derivatives, except for 7. The chalcone possessing one prenyloxy group at C(2'), i.e., 2, was the most active derivative against the three human tumor cell lines (5.9

Prenylated derivatives of baicalein and 3,7-dihydroxyflavone: synthesis and study of their effects on tumor cell lines growth, cell cycle and apoptosis.

Fourteen baicalein and 3,7-dihydroxyflavone derivatives were synthesized and evaluated for their inhibitory activity against the in vitro growth of three human tumor cell lines. The synthetic approaches were based on the reaction with prenyl or geranyl bromide in alkaline medium, followed by cyclization of the respective monoprenylated derivative. Dihydropyranoflavonoids were also obtained by one-pot synthesis, using Montmorillonite K10 clay as catalyst combined with microwave irradiation. In vitro screening of the compounds for cell growth inhibitory activity revealed that the presence of one geranyl group was associated with a remarkable increase in the inhibitory activity. Moreover, for the 3,7-dihydroxyflavone derivatives a marked increase in growth inhibitory effect was also observed for compounds with furan and pyran fused rings. The most active compounds were also studied regarding their effect on cell cycle profile and induction of apoptosis. Overall the results point to the relevant role of the prenylation of flavone scaffold in the growth inhibitory activity of cancer cells.