Application of Internet-based multidisciplinary management in patients with genitourinary cancers in China: A brief introduction to a new model of healthcare service for cancer survivors during COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has triggered multiple global healthcare system crises. Apart from the pandemic itself, the travel restriction and social distance policy for the purpose of epidemic control has cast a shadow on the management of cancer survivors. Cancer survivors suffered a double blow from both the epidemic and cancer. To deal with the challenge, we explored a new Internet-based patient management model. This model has overcome the limitation of time and space and thus can help oncologists to provide remote multidisciplinary healthcare services for cancer survivors. These patients can get high-quality cancer management from multidisciplinary experts without too much transportation. This model has been applied in patients with genitourinary cancers and proved to be effective and efficient. Our study demonstrated that more patients benefited from this model during the pandemic of COVID-19, especially in those affected heavily by COVID-19. These results suggested that it can also give insight into the management of other cancer survivors in China. Given the long-term impact of the COVID-19 pandemic, we would like to introduce our new model of healthcare service and the application of Internet-based multidisciplinary management to our global peers and medical industries to help their cancer survivors who are delayed in treatment due to the COVID-19 pandemic.

Tenofovir-Amino Acid Conjugates Act as Polymerase Substrates-Implications for Avoiding Cellular Phosphorylation in the Discovery of Nucleotide Analogues.

Nucleotide analogues are used for treating viral infections such as HIV, hepatitis B, hepatitis C, influenza, and SARS-CoV-2. To become polymerase substrates, a nucleotide analogue must be phosphorylated by cellular kinases which is rate-limiting. The goal of this study is to develop dNTP/NTP analogues directly from nucleotides. Tenofovir (TFV) analogues were synthesized by conjugating with amino acids. We demonstrate that some conjugates act as dNTP analogues and HIV-1 reverse transcriptase (RT) catalytically incorporates the TFV part as the chain terminator. X-ray structures in complex with HIV-1 RT/dsDNA showed binding of the conjugates at the polymerase active site, however, in different modes in the presence of Mg2+ versus Mn2+ ions. The adaptability of the compounds is seemingly essential for catalytic incorporation of TFV by RT. 4d with a carboxyl sidechain demonstrated the highest incorporation. 4e showed weak incorporation and rather behaved as a dNTP-competitive inhibitor. This result advocates the feasibility of designing NTP/dNTP analogues by chemical substitutions to nucleotide analogues.