主要研究 今天

大流行的结束似乎遥遥无期, scientists are still very focused on finding new or alternative drugs to treat and stop the spread of COVID-19. 这是一项史无前例的研究, 主要研究 researchers found that using an existing drug compound in a new way, 被称为药物再利用, could be successful in blocking the activity of a key 酶 of the coronavirus, 或“非典”-CoV-2, 会导致COVID-19.

“The goal was to slow or prevent the spread of the virus by using a strategic therapeutic that could possibly disrupt key steps in the viral life cycle at the molecular level, like the first contact with a healthy cell or the first step in replicating within an infected cell,” 哈瑞Vashisth化学工程副教授. Vashisth的Ph值.D. 22岁的学生Jacob Andrzejczyk是这项研究的主要作者.

在 研究, 最近发表在《澳门葡京网赌游戏》杂志上, 函数, 和生物信息学, 研究人员开始瞄准一种导致COVID-19的关键酶, 称为主蛋白酶M^箴, which has become a primary target of intense research and therapeutic development because it is essential for the virus to replicate. 在这种情况下, they explored the inhibiting 箴perties of a derivative of the potent chemical compound known as thiadiazolidinones, 或TDZD, which are already being studied as a potential treatment for neurological disorders such as Parkinson’s disease.

“The goal was to slow or prevent the spread of the virus by using a strategic therapeutic that could possibly disrupt key steps in the viral life cycle at the molecular level.”

研究ers used a specific TDZD compound, known as CCG-50014, to target M^箴, which acts like a molecular scissor by cutting up long chains of polypeptide 箴teins of the virus into smaller component 箴teins. These smaller segments can fold and mature to form new virus particles. Using molecular dynamics simulations combined with laboratory experiments, the researchers determined that TDZD compound was able to inhibit the M^箴 酶.

“冠状病毒, 像COVID-19, are a notorious group of infectious agents that include a large class of viruses with RNA genomes, 类似于人类的DNA基因组, that depend on well-organized 箴tein structures crucial for viral growth and replication,瓦希什说. “These viruses can develop rapid defenses at the cellular level by orchestrating these layers, 或者折叠机制, 在病毒蛋白质中，关键是找到一种方法来关闭它们.”

众所周知，RNA病毒会引起季节性流行病, 就像流感, and can appear as novel virus strains with high fatality rates (COVID-19, “非典”, 寨卡和埃博拉). 研究人员表示，需要一种替代药物的开发管道, 而不是将新药推向市场的密集过程, is illustrated by the high infection rate of COVID-19 (compared to previous coronaviruses) and is important for a long-term effective response to new and reoccurring outbreaks.

In addition to Vashisth and Andrzejczyk, additional 主要研究 co-authors on the 研究 are Krisztina巴尔加, 分子副教授, 细胞和生物医学科学, graduate students Katarina Jovic and Logan Brown and undergraduate researcher Valerie Pascetta ’22, 都在分子中, 细胞和生物医学科学.

This research was supported by 格兰特s from the National Institutes of 健康 under award numbers R35GM138217, P20GM113131, 和国家科学基金会，项目编号为OIA-1757371. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. Vashisth和Varga最初的合作部分是由a资助的 主要研究合作研究卓越 格兰特.