The COVID-19 pandemic and the potential treatment of the novel coronavirus SARS-CoV-2.

Coronavirus SARS-CoV-2 is a novel coronavirus and the seventh that can infect human beings and result in severe and acute respiratory syndrome and deaths. Currently, the world is undergoing a global health emergency due to the SARS-CoV-2 pandemic. As of May 18, SARS-CoV-2 has spread to over two hundred countries and infected more than 4.8 million people, resulting in over 300,000 deaths since the first case of a novel pneumonia (COVID-19) patient was discovered in Wuhan, China at the end of December 2019. Currently, there are no effective and/or approved targeting drugs for it though various supportive therapy drugs such as small molecule drugs, vaccines, antibodies and even Chinese herb medicines have been used in the treatment of the first-line patients. However, certain drugs such as remdesivir and S416 are under clinical investigation and may become therapeutic drugs. In this article, we review and discuss SARS-CoV-2, its person-to-person transmission, genomics and proteomics, and the potential for drug development.

The antimicrobial peptides and their potential clinical applications.

Nowadays, the bacterial drug resistance leads to serious healthy problem worldwide due to the long-term use and the abuse of traditional antibiotics result in drug resistance of bacteria. Finding a new antibiotic is becoming more and more difficult. Antimicrobial peptides (AMPs) are the host defense peptides with most of them being the cationic (positively charged) and amphiphilic (hydrophilic and hydrophobic) α-helical peptide molecules. The membrane permeability is mostly recognized as the well-accepted mechanism to describe the action of cationic AMPs. These cationic AMPs can bind and interact with the negatively charged bacterial cell membranes, leading to the change of the electrochemical potential on bacterial cell membranes, inducing cell membrane damage and the permeation of larger molecules such as proteins, destroying cell morphology and membranes and eventually resulting in cell death. These AMPs have been demonstrated to have their own advantages over the traditional antibiotics with a broad-spectrum of antimicrobial activities including anti-bacteria, anti-fungi, anti-viruses, and anti-cancers, and even overcome bacterial drug-resistance. The natural AMPs exist in a variety of organisms and are not stable with a short half-life, more or less toxic side effects, and particularly may have severe hemolytic activity. To open the clinical applications, it is necessary and important to develop the synthetic and long-lasting AMP analogs that overcome the disadvantages of their natural peptides and the potential problems for the drug candidates.

Drug discovery and drug marketing with the critical roles of modern administration.

Drug research and development is a long-term and complicated process with the involvement of multidisciplinary, multi-sector cooperation and regulations of the Food and Drug Administration (FDA). It is of high risk, high cost, high benefit and time-consuming. Therefore, the drug administration and management is extremely necessary and useful. We discussed the whole process including laboratory study, target determination, drug discovery and screening, leading compound and optimization, preclinical and clinical trials, FDA approval and marketing. Actively exploring and applying modern administration and innovative management technology, we can scientifically and effectively enhance the discovery of new drug research and development, and strengthen the supervision of drug market. In recent years, innovation such as artificial intelligence has been applied to drug discovery and drug administration. We further analyzed the possibility of applying management technology to reduce risks, generate profits and benefit patients in the whole process of new drug research and development. In conclusion, drug administration and management plays critical roles in modern drug research and development, and the new technology can be helpful for drug launching.

Effects of camptothecin on tumor cell proliferation and angiogenesis when coupled to a bombesin analog used as a targeted delivery vector.

The camptothecin-bombesin conjugate termed DC-51-43, as a novel targeted drug delivery system, was examined in over 10 human tumor cell lines and shows a potent antiproliferative activity. This conjugate has also demonstrated its antitumor activity in our previous experiments. In our present study, we evaluate this conjugate for its antiangiogenic activity by in-vitro and in-vivo experiments. The camptothecin-bombesin conjugate and free camptothecin show potent in-vitro inhibitory activities of cell adhesion to various extracellular matrix components and integrins alphaVbeta3 and alphaVbeta5, not beta1/alphabeta1. This conjugate displays inhibitory activity to cell migration and invasion at concentrations of 10 micromol/l or above. This conjugate is also effective against in-vitro capillary-like tube formation of endothelial cells (at 40 micromol/l), and in-vivo angiogenesis as seen by blocking the spread of host mice endothelial cells into matrigel plugs. These experimental results support the fact that the camptothecin-bombesin conjugate has therapeutic activities against angiogenesis. By binding to bombesin receptor-expressing sites, this bombesin analog, consisting of 11 amino acids, is potentially a novel delivery vector for nonspecific cytotoxic agents.