COVID-19: molecular targets, drug repurposing and new avenues for drug discovery

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infection that may break the healthcare system of several countries. Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. Finally, we also discuss patent protection issues, cost effectiveness and scalability of synthetic routes for some of the most studied repurposing candidates since these are key aspects to meet global demand for COVID-19 treatment.

New advances in the discovery of anti-enterovirus-71 agents / 药学学报

In recent years, enterovirus infection has become a frequent epidemic and developed into an important public health problem. For example, hand-foot-mouth disease has become a common infection among children in China. Hand-foot-mouth disease (HFMD) has been spreading globally since 1997, especially in the Asia-Pacific region. Enterovirus 71 (EV71) is one of the main pathogens causing HFMD. And now there is no drug available to treat EV71 infection. This review summarizes the research progress of anti-enterovirus-71 drugs from the perspective of medicinal chemistry.

Advances in human cytomegalovirus inhibitors / 药学学报

At present, the anti-HCMV (human cytomegalovirus) drugs have some problems, such as moderate activity, poor bioavailability, which urge people to develop new anti-HCMV drugs. With the continuous study on the pathogenesis and biological characteristics of HCMV and the rapid development of new drug design strategies, new generation of anti-HCMV targets and drugs have been identified. This review selects the most representative research examples in recent years, and summarizes the new targets and research progress of anti-HCMV drugs from the perspective of medicinal chemistry.

Progress on AIDS drug targets and small molecule inhibitors / 药学学报

The difficulty to eradicate the HIV-1, off-target effects together with the rapid emergence of multidrug-resistant strains have created an urgent need for more potent and less toxic therapies against other targets of HIV virus. From the point of view of medicinal chemistry, we summarizes and discusses current endeavours towards the discovery and development of novel inhibitors with various scaffolds or distinct mechanisms of action, and also provides examples illustrating new methodologies in medicinal chemistry that contribute to the identification of novel antiretroviral agents.

On the origin of life

The origin of life is a very rich field, filled with possibilities and ripe for discovery. RNA replication requires chemical energy and vesicle division is easy to do with mechanical energy. These requirements point to a surface lake, perhaps at some time following the period of concentrated cyanide chemistry that gave rise to nucleotides, amino acids and (maybe) fatty acids. A second requirement follows specifically from the nature of the RNA replication cycle, which requires generally cool to moderate temperatures for the copying chemistry, punctuated by brief periods of high temperature for strand separation. Remarkably, lakes in a geothermal active area provide just such a fluctuating temperature environment, because lakes similar to Yellowstone can be generally cool (even ice covered in winter), but they contain numerous hydrothermal vents that emit streams of hot water. Protocells in such an environment would occasionally be swept into these hot water streams, where the transient high temperature exposure would cause RNA strand separation. However, the protocells would be quickly mixed with surrounding cold water, and would therefore cool quickly, before their delicate RNA molecules could be destroyed by heat. Because of the combination of favorable chemical and physical environments, this could be the most likely scenario for the early Earth environment that nurtured the origin of life.

El origen de la vida es un campo lleno de posibilidades, listas para ser descubiertas. Basados en lo conocido sobre modelos de sistemas de membranas y sobre ARN, se comienza a deducir algunas características necesarias del entorno inicial. La replicación del ARN requiere energía química y la división de la vesícula es fácil de hacer con la energía mecánica. Estos requisitos apuntan a la superficie de un lago, en algún momento después del período en que la química del cianuro concentrado dio origen a los nucleótidos, aminoácidos y (tal vez) ácidos grasos. Un segundo requisito surge de la naturaleza del ciclo de replicación del ARN, que requiere temperaturas moderadas para la química de la copia, interrumpidas por breves períodos de alta temperatura para la separación en hebras. Solo lagos en una zona de actividad geotérmica proporcionan un ambiente de temperatura tan oscilante, lagos similares a Yellowstone pueden ser frescos (cubiertos de hielo en invierno), pero contienen numerosas fuentes hidrotermales que emiten chorros de agua caliente. Las protocélulas, en un ambiente así, de vez en cuando serían barridas en estas corrientes de alta temperatura, que podrían causar la separación transitoria de ARN de cadena. Pero las protocélulas serían mezcladas con rapidez en la zona de agua fría, y enfriarse antes de que sus delicadas moléculas de ARN fueran destruidas por el calor. La combinación de estos ambientes químicos y físicos favorables serían el escenario más probable del medio ambiente de la Tierra temprana que nutrió el origen de la vida.