张绪穆：年轻学者一定要有开创一个领域的磅礴大气

文/吴星铎 译/张佳艺

“解决科学难题，同时造福人类。”“教授做出来的成果，不仅能放在书架上，更能放在货架上，书架货架都要上。”这是采访张绪穆院士印象最深的两句话。

2023年5月28日上午，第二期国际院士讲堂开讲，张绪穆院士带来《中国健康医药产业化道路：不对称催化技术及在制药工业中的应用》的主题分享。

在国际院士讲堂的前一天，张绪穆院士接受了笔者专访。在小分子药领域、手性现象中自由徜徉，让笔者对张院士的学者风范、厚重睿智印象深刻，并被深深触动和感染。

从诺奖到师门缘分

话题从2022年刚刚获得诺贝尔化学奖的美国化学家巴里·夏普莱斯（K.Barry Sharpless）展开。夏普莱斯是张绪穆的同门师兄，是第二位两次获得诺贝尔化学奖的科学家。

“夏普莱斯在2001年获得的诺贝尔奖是关于‘不对称化学合成’，这次是关于‘点击化学和生物正交合成’。”张绪穆介绍说，当年第一次获得诺奖时夏普莱斯已经年满60岁，张绪穆受邀参加了他在圣地亚哥举办的60岁生日会，这位师兄并没有止步于其在手性化学领域的成就，很快就开启了一个新的方向，进入生物领域。“短短20年时间，又开辟了一个全新的研究领域，这是科学创新的典范。”张绪穆说。

“Solve scientific problems while benefiting mankind.”“The professors’ achievements are not only on the bookshelves but also on the goods shelves.” These two impressive sentences come from an interview with academician Zhang Xumu.

On the morning of May 28, 2023, academician Zhang Xumu delivered a theme presentation of “The Road to China’s Health Medicine Industrialization:Asymmetric Catalysis Technology and its Application in the Pharmaceutical Industry” on the second phase of the International Academician Forum.

The day before the International Academician Forum,academician Zhang Xumu received an exclusive interview with the author. In the small molecules and chiral phenomenon field, the author was deeply impressed by his scholarly style and wisdom and was deeply touched and infected.

From Nobel Prize to predestination of taking the same master

The conversation started with K. Barry Sharpless, an American chemist who won the Nobel Prize in Chemistry in 2022. Zhang Xumu studied under the same master with Sharpless who won the Nobel Prize in Chemistry twice.

“The Nobel Prize Sharpless won in 2001 was for‘Asymmetric Chemical Synthesis’ and this time for ‘Click Chemistry and Bioorthogonal Synthesis’.” Zhang Xumu explained that Sharpless had turned 60 when he first won the Nobel Prize. Zhang Xumu was invited to his 60thbirthday party in San Diego. Sharpless didn’t stop at the accomplishments in chiral chemistry but soon opened up a new biology chapter. “To open up another wholly new field of research in just 20 years is an example of scientific innovation.” Zhang Xumu said.

夏普莱斯与美国化学家卡罗琳·贝尔托西（Carolyn P.Bertozzi）、丹麦化学家莫滕·梅尔达（Morten P.Meldal）共享了2022年的诺贝尔化学奖。在张绪穆看来，“夏普莱斯因为之前已经获得了诺贝尔奖，他的影响力是最大的，贝尔托西排在第二。梅尔达独立做出了与夏普莱斯差不多同样的工作。”

张绪穆认为，“点击化学”（Click Chemistry）的名称体现了师兄一贯主张的“大道至简”。“点击化学”又被称为“链接化学”，实质上是通过链接各种小分子来合成复杂的大分子，就像上车扣上安全带一样，便捷有效。夏普莱斯之所以有这样的构想，其实也是来自大自然的启发。大自然就像一个有着神奇能力的化学家，它通过少数的单体小构件，合成丰富多样的复杂化合物。

张绪穆说，“点击化学”的奠基性论文于2000年8月提交给《德国应用化学》杂志，没有一个评审专家认为该篇文章应该被接收发表，经过申诉后杂志的主编愿意推翻负面评论，2001年5月《点击化学：通过几个好的反应实现分子功能》发表。该篇文章是目前合成化学领域引用量最高的一篇论文。“众人皆醉我独醒。一定要坚持真理。真理有时候就是掌握在少数人手上，一定要对自己有信心。”张绪穆说。

在张绪穆看来，夏普莱斯“大道至简”的研究理念使得他总能抓住科学问题的核心，做出最简单、最有用的科研成果。夏普莱斯的“KISS”（KISS：Keep it Simple, Stupid.），正是“大道至简”理念的体现。

另一位对张绪穆有影响的师兄，是2005年因为烯烃复分解反应获得诺贝尔化学奖的罗伯特·格拉布斯（Robert H.Grubbs），“成立公司容易，要赚钱不容易。要有情怀，对世界产生巨大的影响力。此外，一定要把知识产权搞干净。”格拉布斯的肺腑之言，让张绪穆受益匪浅。

Sharpless shared the 2022 Nobel Prize in Chemistry with American chemist Carolyn P. Bertozzi and Danish chemist Morten P. Meldal. In Zhang Xumu’s opinion, “Sharpless had the most influence because he had already won the Nobel Prize. Bertozzi came in second. Meldal independently did almost the same work as Sharpless.”

According to Zhang Xumu, “Click Chemistry” reflects the “Greatest truths always turn out to be simple.” “Click Chemistry,” also known as “Link Chemistry,” is essentially the synthesis of complex macromolecules by linking various small molecules, which is as convenient and effective as buckling up in a car. The reason why Sharpless has such a conception is inspired by nature. Nature is like a chemist with the magical ability to synthesize a wide variety of complex compounds through a small number of small monomer components.

Zhang Xumu said the seminal “click chemistry”paper submitted to theAngewandte Chemie International Editionin August 2000 was declined for publication. After appeals, the editor-in-chief was willing to override the negative comments and publish Click Chemistry: Molecular Functionality through a Few Good Reactions in May 2001.The article is now one of the most highly cited papers in synthetic chemistry. “Keep sober, especially when others are confused. Always stick to the truth. A minority sometimes seizes the truth, so be confident in oneself.” Zhang Xumu said.

In Zhang Xumu’s opinion, Sharpless’s research philosophy of “greatest truths always turn out to be simple”has enabled him to grasp the core of scientific problems and make the most straightforward and valuable results.Sharpless’s “KISS” (KISS: Keep it Simple, Stupid.) is the embodiment of the concept that “greatest truths always turn out to be simple”.

Another senior fellow apprentice who influenced Zhang Xumu is Robert H. Grubbs, who won the Nobel Prize in Chemistry in 2005 for the olefin complex decomposition reaction. “Setting up a company is easy but uneasy to make money. Be full of emotion and have a huge impact on the world. Additionally, keep the intellectual property clear.”Grubbs’s heartfelt words benefited Zhang Xumu a lot.

In November 2015, at the invitation of Zhang Xumu,Grubbs was appointed chairman of the Academic Advisory Board of the Department of Chemistry of the Southern University of Science and Technology (SUSTech) and planned to establish the Grubbs Institute at SUSTech, with Grubbs as the honorary dean, and Zhang Xumu as the founding executive dean. Based on SUSTech, the institute will set up a new medicine research center, a new material research center, and a new energy research center, vigorously introduce high-end talents from all over the country and even the world, and carry out subversive original innovation in the field of basic research, to vigorously promote the basic research and industrial development of Shenzhen and even China in the areas of new medicine, new materials, and new energy.

2015年11月，应张绪穆邀请，格拉布斯受聘南方科技大学化学系学术顾问委员会主席，并筹划在南科大建立格拉布斯研究院，格拉布斯出任荣誉院长，创始执行院长由张绪穆担任。研究院以南方科技大学为依托，设置新医药研究中心、新材料研究中心、新能源研究中心，大力引进全国乃至全世界的高端人才，在基础研究领域进行颠覆性原始创新，强力推动深圳乃至中国在新医药、新材料和新能源等领域的基础研究与产业发展。

为表彰他们为深圳发展和国际交流合作所作出的巨大贡献，6名来自各个领域的有识之士获选为“2016时代深士”，张绪穆教授是教育界、科学界唯一入选者。源于他促成了格拉布斯与深圳的“联姻”——深圳格拉布斯研究院在南方科技大学落地。何为“深士”？“谙政识商，照烛国际，集天下智慧，谋鹏城腾飞。”

“这份荣耀更加激发了我们回国创新创业的激情。”张绪穆说。

“夏普莱斯和格拉布斯是詹姆斯·科尔曼（James P.Collman）教授20世纪70年代的弟子，我是90年代的弟子，当年在他门下学习的时候，他也经常嘱咐我们，把两位师兄作为榜样。”张绪穆回忆说。

“科尔曼是一代宗师，他今年已经90岁了，我刚刚去斯坦福大学见了他。他对我目前的成就赞誉有加，对我寄予厚望。”谈到对导师印象最深刻的一句话，张绪穆回忆，“一个人学术的成就可能体现在文章上，但更重要的是体现在你培养的学生上。”科尔曼教授的话深深影响着张绪穆，“这些年来，我非常重视人才培养，正是在践行导师的教诲。”

In recognition of their significant contributions to Shenzhen’s development and international exchange and cooperation, six insightful talents from various fields were selected as the “Shentlemen of the Year 2016”, and Prof.Zhang Xumu was the only one chosen from the education and science sectors, and this is because he facilitated the“marriage” between Grubbs and Shenzhen—the Shenzhen Grubbs Research Institute has landed on the ground in SUSTech. What is “Shentlemen”? “Understand politics and business; light up the international world; gather the world’s wisdom; seek general take-off.”

“This honor inspires us to return to China to innovate and start a new business.” Zhang Xumu said.

“Sharpless and Grubbs are the disciples of Prof. James P.Collman in the 1970s, and I was a disciple in the 1990s. When I studied under Prof. James P. Collman, he often instructed me to take the two elder brothers as role models.” Zhang Xumu recalled.

“Collman is a master of his generation. He is 90 years old now. I just went to Stanford University to meet him.He was very complimentary about my achievements and had high hopes for me.” Regarding the mentor’s words that impressed him most, Zhang Xumu recalled, “One’s academic achievements may be reflected in the articles, but more importantly in the students you cultivate.” Prof. Collman’s words profoundly influenced Zhang Xumu. “Over the years, I have attached great importance to talent cultivation,precisely practicing my mentor’s words.”

From chiral phenomenon to asymmetric catalysis

The chemical phenomenon behind the Thalidomide event that shocked the world in 1961 was the phenomenon of chirality.

Back then, an anti-pregnancy drug was widely used in Europe and Japan. It has two different structures, R and S.Just like our right and left hands, although they seem to be the same, they have other forms. The R-configuration of it is safe, while the S-configuration causes fetal malformations.It is as if it looks as similar as the right and left hands,while the right hand is good and the left hand is poisonous.However, the scientific community did not realize that the two conformations have different physiological activities in the human body. This oversight resulted in the heartbreaking fact of tens of thousands of “thalidomide babies,” i.e., the deformed newborns, in Europe and Japan. To obtain the desired results,asymmetric catalytic techniques were developed.

2023年5月28日，国际院士讲堂第二期“中国健康医药产业化道路：不对称催化技术及在制药工业中的应用”嘉宾合影

从手性现象到不对称催化

1961年震惊世界的“反应停事件”，背后隐藏的化学现象就是手性现象。

当年，一种抗妊娠反应药物在欧洲和日本广泛使用。它有R和S两种不同结构，就像我们的左右手，虽然看似一样，但却有着不同的结构。其中的R构形是安全的，而S构形会导致胎儿畸形。好比说看起来如左右手一般相似，右手是好的，左手却是有毒的。但此前科学界没有意识到两种构形在人体内有不同的生理活性。而这一疏忽在欧洲和日本造成了数万“海豹儿”，也就是畸形新生儿，令人痛心疾首。为了获得人们想要的结果，于是有了不对称催化技术。

作为一名科普爱好者，手性现象也成为采访张院士前后笔者最好奇的话题，为什么地球人的氨基酸都是左手手性，糖都是右手手性，在遥远的其他星球上，会不会有氨基酸的手性是和我们完全相反的存在？“手性的起源和人的起源一样。人从哪里来，手性从哪里来？这个现象有很多假设。手性起源是《科学》杂志上的100个最具挑战性的问题之一，至今我们也不知道它怎么来的，谁要是把手性起源搞清楚了，肯定也能拿诺贝尔奖。”张绪穆笑着说。

As a science enthusiast, the chiral phenomenon has also become the most curious topic of the interviewers: Why are all the amino acids of humanity left-handed chirality, and all the sugars right-handed chirality? Will there be the existence of amino acid chirality utterly opposite to ours on other distant planets “The origin of chirality is the same as the origin of man. Where does man come from, and where does chirality come from? There are many hypotheses for this phenomenon.The origin of chirality is one of the 100 most challenging questions inSciencejournals, and so far, we don’t know how it came about. Whoever determines the origin of chirality will also get a Nobel Prize.” Zhang Xumu said with a smile.

“How do you get a single chirality? It used to be measured.Both chirality exist, as if using a left or right glove, leaving the one you need and throwing away the other you don’t want. But that would waste half the material.” Zhang Xumu patiently explains, “Producing a single chirality can be controlled by a chiral ligand, like having a mold that directly turns a flat structure into the desired chiral structure. This is asymmetric catalysis, and asymmetric hydrogenation is the most effective.”

“Asymmetric hydrogenation is essential for efficiently synthesizing chiral APIs and their intermediates. More than60% of small molecule drugs are chiral, of which 60% can be obtained by asymmetric hydrogenation.” Zhang Xumu said.

“怎么获得单一手性？以前是测分，这两种手性都有，好比用一只左手或者右手的手套，把需要的留下，另一种不要的扔掉。不过这就会浪费掉一半的材料。”张绪穆耐心地解释，“生产单一手性可以靠手性配体来控制，这好比有一个模子，直接把平面的结构变成想要的手性结构，这就是不对称催化，而不对称氢化是其中最有效的。”

“不对称氢化对于手性原料药及其中间体的高效合成至关重要。小分子药物60%以上为手性药物，其中60%可以通过不对称氢化得到。”张绪穆说。

张绪穆在不对称氢化和手性膦配体研究领域取得了丰硕的研究成果。他开发的手性工具箱广泛应用于不对称氢化、不对称氢甲酰化反应等领域，具有重要的国际影响力，因此他成为荣获美国化学会亚瑟·科普学者奖（Arthur C.Cope Scholar Awards）的首位来自中国大陆的学者。

“2000年前后我提出3S概念，反应要快（Speed），选择性（Selectivity）好，还有一个是催化剂稳定性（Stability）好，有自主知识产权，能达到百万转化数，甚至千万转化数，是我们追求的目标。”张绪穆说。

他开发的张烯炔环异构化反应，是以华人学者命名的少数人名反应之一，对药物绿色合成产生了重大影响。据了解，全世界人名反应有200个左右，华人人名反应在各种教科书中有5个左右。

“教科书当中的人名反应，就像数学的定理一样，这是我们科学家得到公认之后的一个荣耀。终于有一个以我的名字来命名的国际公认的反应了。”张绪穆分享当时的心情，他笑言：“当然我还想有第二个。”基于师兄夏普莱斯“大道至简”的启发，张绪穆将自己最新的不对称催化科研成果凝结成一个名称“@Catalysis”，也就是“@催化”。笔者期待与读者们一起，见证“@催化”的成熟、推广与丰硕的成就。

Zhang Xumu has achieved fruitful research results in asymmetric hydrogenation and chiral phosphine ligand research. The chiral toolbox he developed is widely used in asymmetric hydrogenation and asymmetric hydroformylation reactions, which has a significant international influence. Thus, he became the first scholar from Chinese mainland to win the Arthur C. Cope Scholar Awards of the American Chemical Society.

“Around 2000, I put forward the 3S concept: high“Speed” of reaction, good “Selectivity,” good “Stability”of catalyst. We pursue owning independent intellectual property rights and reaching millions or even ten million conversions.” Zhang Xumu said.

The Zhang Enyne Cycloisomerization that he developed is one of the few human-named reactions named after Chinese scholars and has significantly impacted the green synthesis of drugs. It is known that there are about 200 human-named reactions around the world, and there are about five Chinese human-named reactions in various textbooks.

“Like a theorem in mathematics, a reaction named after a person’s name in the textbooks is an honor for scientists once we are recognized. Finally, there is an internationally recognized reaction named after me.” Sharing his feelings at the time, Zhang Xumu laughed, “Of course I want a second one.” Based on the inspiration of Sharpless’s “greatest truths always turn out to be simple”, Zhang Xumu condensed his latest asymmetric catalytic achievements into a single name,“@Catalysis.” It is worth looking forward to witnessing the maturity, popularization, and fruitful achievements of “@Catalysis.”

International peers have highly evaluated his research results: Mr. Zhang’s research on chiral ligands for asymmetric hydrogenation is an essential step toward practical asymmetric catalysis. His development of catalysts for the highly enantioselective hydrogenation of fatty ketones has impacted the asymmetric hydrogenation of simple ketones comparable to that of Ryoji Noyori, the 2001 Nobel Laureate in Chemistry.

Scientist entrepreneurship: On bookshelves as well as goods shelves

In 1999, Zhang Xumu went to the laboratories of two Nobel Prize winners, his senior fellow apprentices,for academic vacations. There, he found that they paid particular attention to the practical value of academics,which inspired Zhang Xumu a lot. So, Zhang Xumu started his path of “Scientist Entrepreneurship”.

国际同行高度评价了他的研究成果：张先生用于不对称氢化的手性配体研究，向实用的不对称催化迈出了重要的一步。他发展的用于高对映选择性地氢化脂肪酮的催化剂，在简单酮的不对称氢化方面的影响力，与2001年诺贝尔化学奖获得者野依良治（Ryoji Noyori）不相上下。

科学家创业：书架货架都要上

1999年，张绪穆去两位诺贝尔奖获得者兼同门师兄的实验室进行学术休假，发现师兄们对学术的实践价值特别重视，这给了张绪穆很大启发，于是张绪穆开启了自己的“科学家企业创始人”之路。

张绪穆分享说：“其一，办公司更有利于自己做一些化学基本原理的创新；其次，在高校里，用我们的聪明才智创造新物质，这可以算是上了书架，而如果形成的产品能够转化，那就算上了货架；最后，还有一个很重要的是培养人才，培养产学结合的人才。”张绪穆认为，一流大学并不是关起门来做学术，做出来的成果不仅能放在书架上，还能放在货架上，展示科学研究的社会效益，为社会和人类创造价值。他长期致力于发展高效、高选择性不对称催化反应，利用自己原创的手性配体工具箱为技术平台，以重大药物合成为产业化突破口，开发有自主知识产权、安全、环保、低成本、高质量的药物绿色合成新工艺。他先后成立了凯瑞斯德生化（苏州）有限公司（以下简称凯瑞斯德）、凯特立斯深圳科技有限公司（以下简称凯特立斯）和深圳安泰维生物医药有限公司（以下简称安泰维）三家公司。

2023年5月28日，张绪穆在国际院士讲堂进行主题分享

Zhang Xumu shared, “Firstly, running a company is more conducive to doing some innovation in the basic chemistry principles. Secondly, in the university, using our ingenuity to create something new can be considered to be on the bookshelves. However, if the products can be transformed, they will be considered on the goods shelves.Lastly, it is important to cultivate talents who integrate production and learning.” Zhang Xumu believes that the first-class university makes achievements that should not only be put on the bookshelves but also on the goods shelves,rather than academics indoors, so that it benefits scientific research and creates value for society and humanity. He has long been committed to the development of efficient and highly selective asymmetric catalytic reactions, using his original chiral ligand toolbox as a technology platform,taking major drug synthesis as an industrialization breakthrough, and developing new processes for green synthesis of drugs with independent intellectual property rights, safe, environmentally friendly, low-cost and high quality. He has successively established three companies,namely “Chiral Quest (Suzhou) Co., Ltd. (from now on referred to as ‘Chiral Quest’),” “Kaitelis (Shenzhen)Technology Co., Ltd. (from now on ‘Catalyst Technology’),”and “Shenzhen Antiv Pharma Co., Ltd. (from now on as‘Antiv’).”

Founded in 2008, Chiral Quest has already produced more than 20 new process routes with an annual production capacity of more than 5 tons. It makes hundreds of tons of pharmaceutical intermediates and APIs yearly related to the medication needs of hundreds of millions of patients worldwide. “Chiral Quest is the first company I founded,gathering my years of scientific research. We have an R&D headquarters in Suzhou, a production base in Jiangxi, and sales offices in the UK and India. We look forward to listing on the Sci-Tech Innovation Board shortly.” Zhang Xumu said.

凯瑞斯德成立于2008年，已有20多个年产大于5吨的新工艺路线投入生产，每年生产几百吨医药中间体和原料药，关乎全世界数亿患者的用药需求。“凯瑞斯德是我成立的第一家公司，聚集了我多年的科研成果。苏州有研发总部，江西有生产基地。我们在英国、印度都有销售办公室，期待在不久的将来在科创板上市。”张绪穆说。

2015年，以张绪穆为主导的团队获批深圳市海外高层次人才“孔雀团队”，成立凯特立斯，并于2018年正式启动项目研发，目前已取得沙库必曲、尼古丁、西那卡塞、苯福林、依折麦布、孟鲁斯特等10多种大品种药物新工艺路线的重大突破。“凯特立斯是一个平台公司，轻资产模式，赋能产业。”张绪穆解释说。

至于2021年创立的抗病毒新药公司安泰维，“这家公司在我看来是我们孵化的跨界新星。”张绪穆说。

“顶天立地、国家需求、原始创新”是这位科学家创始人一以贯之的指导思想。“我们要面向世界科学前沿、面向经济主战场、面向国家重大需求、面向人民生命健康，顶天立地，国家需求，原始创新。”张绪穆说，他尤其强调原始创新。“只有原始创新才是‘卡住脖子’的，你要是跟在别人后面亦步亦趋，你始终在给别人抬轿子。”原始创新也就是罗伯特·兰格原则中的专利。

张绪穆（右一）与2001年、2022年诺贝尔化学奖获得者巴里·夏普莱斯（K.Barry Sharpless）（中）合照

除了师兄的影响，张绪穆的科学家创业理念也受到麻省理工学院著名科学家与企业家罗伯特·兰格（Robert Langer）的影响。采访中，张绪穆分享了罗伯特·兰格的“3个P”原则也就是平台（Platform）、学术文章（Paper）、专利（Patent），“再加上良好的创新生态，才能让科学家的研究成果加快向市场转化。”

In 2015, the team led by Zhang Xumu was approved by Shenzhen’s “Peacock Team” of overseas high-level talents,and kaitelis was set up. It formally launched the project research and development in 2018 and has made a significant breakthrough in the new process of more than ten large varieties of drugs, such as sakubitril, nicotine, cinacalcet,benfotiamine, ezetimibe, and mengluste. “kaitelis is a platform company with an asset-light model to empower the industry.” Zhang Xumu explained.

As for Antiv, a new antiviral drug company founded in 2021, “This company is a cross and a rising star that we have incubated, I think.” Zhang Xumu said.

“An indomitable spirit, national needs, original innovation” is the consistent guiding principle of this scientist entrepreneur. “We have to face the world’s scientific frontiers, face the main battlefield of the economy, face the country’s major needs, and face the people’s life and health.We should pursue an indomitable spirit, national needs, and original innovation.” Zhang Xumu said that he particularly emphasized original innovation. “Only the original innovation is the bottleneck. If you always follow others,you do a hard but resultless job.” Original innovation is also known as patents in Robert Langer’s principles.

新冠口服药“SHEN26”正在进行时

“目前我们正在进行新型冠状病毒小分子口服药SHEN26的临床研究，已在全国20多个中心开展Ⅲ期临床试验，并在继续新增临床试验中心的受试者入组，进展顺利。期待今年内能上市。”张绪穆说。

2020年年初新冠疫情暴发以后，张绪穆携团队与中山大学郭德银教授团队开发抗新冠口服药物，化合物“SHEN26”是科技部新冠专项资助的五个小分子抗新冠药物中的一个。

张绪穆介绍说，SHEN26胶囊是一款广谱的RNA依赖性RNA聚合酶（RdRp）抑制剂，实验室数据和相关的研究结果显示，RdRp靶点具有广谱性，对不同新冠病毒变异株均有高效的体外抑制活性，并且具有拓展RSV病毒适应证的潜力。SHEN26胶囊已完成的Ⅱ期临床研究结果显示，与安慰剂组对比，服用SHEN26胶囊后，患者体内的病毒载量下降趋势明显，安全性表现优异。SHEN26胶囊分子式结构设计科学合理、生产工艺成熟高效，有助于降低用药成本，提升患者用药可及性。据了解，SHEN26胶囊更为合理的设计与更为成熟高效的工艺所带来的成本优势，不仅有望为更广大的患者用药提供便利，也将为公司的产品定价带来更大的空间。

最新公告披露，在国内众多在研新冠口服药中，目前安泰维与科兴制药全资子公司深圳科兴药业有限公司合作开发的SHEN26胶囊研发进度已跑在前列。随着Ⅲ期临床试验的顺利开展，待SHEN26胶囊上市后有望凭借良好的临床效果、安全性以及成本优势打开市场，在实现业绩表现的同时，为广大百姓对抗新冠病毒带来更优的选择。

In addition to the influence of his senior, Zhang Xumu’s entrepreneurial philosophy as a scientist was also influenced by Robert Langer, a renowned scientist and entrepreneur at the Massachusetts Institute of Technology(MIT). In the interview, Zhang Xumu shared Robert Langer’s 3P principles, representing Platform, Paper and Patent. “Only with a good innovation ecosystem can it accelerate the transformation of scientists’ research results towards the market.”

COVID-19 oral medicine in progress

“We are currently conducting clinical studies of SHEN26. It has been conducting Phase III clinical trials at more than 20 centers nationwide and is continuing to enroll subjects at additional clinical trial centers. It progresses well. It is expected to be on the market within this year.” Zhang Xumu said.

After the outbreak of COVID-19 in early 2020, Zhang Xumu and Professor Guo Deyin’s team at Sun Yat-sen University developed anti-COVID-19 oral medicine. The compound “SHEN26” is one of the five small-molecule anti-COVID-19 medicines the Ministry of Science and Technology funds.

Zhang Xumu said that the SHEN26 capsule is a broadspectrum RNA-dependent RdRp inhibitor. Laboratory data and research results show that the RdRp target has a broad spectrum, with high affection in vitro inhibitory activity against different COVID-19 variants. It also has the potential to expand the indications of the RSV virus.SHEN26 capsule has completed Phase II clinical study,and the results show that compared with the placebo group, the viral load in the body of the patients who take SHEN26 capsules decreases significantly, and the safety performance is excellent. The molecular structure design of the SHEN26 capsule is scientific and reasonable, and the production process is mature and efficient, which can help reduce the cost of medication and enhance the accessibility to patients. It is understood that the more reasonable design and more mature and efficient process of cost advantages of the SHEN26 capsule is expected to provide convenience for a broader range of patients and the company’s product pricing.

The latest announcement showed that, among the many anti-COVID-19 oral medicines under development in China, the R&D progress of the SHEN26 capsule, which is jointly developed by Antiv and the branch of Shenzhen Sinovac, has ranked first. With the smooth development of phase III clinical trials, SHEN26 capsule is expected to open up the market with good clinical results, safety, and cost advantages. Harvesting good performance brings better choices for the general public to fight against the COVID-19 virus.

“解决科学难题，同时造福人类”

张绪穆认为，更多中国科学家获得诺奖，这是一个时间问题。“只是迟早的事，一般来说，诺奖是认可科学家差不多20年前的工作。中国真正发力在科技创新也就是现在，20年之后我相信会有更多中国科学家拿诺奖。”

笔者问及对年轻学者的建议，张绪穆说：“一定要有开创一个领域的磅礴大气，拥有一棵树比在树上剪一些枝枝叶叶要好。创造力比知识更重要，保持对科学的洞察力，尽快找到自己感兴趣又有能力的方向，独树一帜，开创未来，从0到1，持之以恒。”

“解决科学难题，同时造福人类。”这句话源自张绪穆对巴斯德象限的思考。曾经有一个学生问他，怎样才能成为顶级科学家。他拿出一张还画有几个分子结构的纸，画了一个直角坐标系，说：“横坐标是学术本身，一个精妙的反应、一个复杂数学模型的建立、一个艰难实验的完成都可以让我们站在这个坐标的最右端；纵坐标是它的实践价值，一个能救治病人的特效药、一个能增加粮食产量的新方法都可以使我们处于这个坐标的最上端。然而有些极难的科学问题并不能被广泛应用，而有些改变人们生活方式的发明，其实又不需要太多的高科技。”接着，他用笔重重地点在了坐标系的右上角，说道，“那些同时解决了科技难题又造福人类的才是最顶尖的科学家。”

“我鼓励我的学生继续做这个事情。如果说珠穆朗玛峰是我们要攀登的最高峰，还没到顶，我们还要再继续努力，世上无难事，只要肯登攀，我们还得往前走。”张绪穆说。

而他名字当中的“穆”，正是珠穆朗玛峰的“穆”。

“Solving scientific problems while benefiting mankind”

Zhang Xumu believes that more Chinese scientists will win the Nobel Prize sooner or later. “It’s just a matter of time. Generally speaking, the Nobel Prize is to recognize the work of scientists almost 20 years ago. Now, it is the shot of China’s real science and technology innovation power. After 20 years, I believe there will be more Chinese scientists to take the Nobel Prize.”

The author asked about the advice for young scholars,and Zhang Xumu said, “Young scholars must have the majesty of pioneering. Planting a tree is better than pruning branches and leaves. Creativity is more important than knowledge. Keep the insight of science. Find what they are interested in and good at as soon as possible. Be unique and adhere to pioneering the future from 0 to 1.”

“Solving scientific problems while benefiting mankind.” This sentence originated from Zhang Xumu’s reflection on Pasteur’s quadrant. A student once asked him how to become a top scientist. He took out a piece of paper with a few molecular structures still drawn,drew a right-angle coordinate system, and said, “The horizontal coordinate is the academics itself. A subtle reaction, establishing a complex mathematical model, and completing a difficult experiment can make us stand at the rightmost end of this coordinate. The vertical coordinate is its practical value. A potent medicine that can save a life and a new method that can increase food production can put us at the top of this coordinate. Yet, some challenging scientific problems cannot be widely applied. While some inventions change people’s lifestyle, they don’t require much high technology.” Then, with a heavy point of his pen in the upper right corner of the coordinate system, he said, “Those who simultaneously solve scientific problems and benefit mankind are the top scientists.”

“I encourage my students to keep exploring. If Mount Qomolangma is the highest peak we have to climb, we haven’t reached the top yet. We have to continue to work harder. Nothing is difficult in the world as long as we are willing to go all out. We still have to forge ahead.” Zhang Xumu said.

What’s more, the “Mu” in his name is precisely the“Mu” in “Zhu Mu Lang Ma”(translated name of Mount Qomolangma).