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研究發現,猴痘突變導致病毒迅速傳播,逃避藥物和疫苗

研究發現,猴痘突變導致病毒迅速傳播,逃避藥物和疫苗

資料來源:密蘇里大學 / 2022 年 11 月 4 日/財團法人台灣紅絲帶基金會編譯

 

圖片來源:密蘇里大學

 

猴痘已感染全球 100 多個國家的 77,000 多人,並且與 COVID-19 相似,突變使該病毒變得更強大、更聰明,在其感染更多人的任務中逃避抗病毒藥物和疫苗。

現在,密蘇里大學的一組研究人員已經確定了猴痘病毒中導致其持續傳染性的特定突變。 這些發現可能會導致多種結果:用於治療猴痘患者的現有藥物的改良版本,或開發新藥以解決當前的突變,以提高其在減輕症狀和病毒傳播方面的有效性。

MU 獸醫學院教授兼 Christopher S. Bond 生命科學中心首席研究員 Kamlendra Singh 與 Shrikesh Sachdev、Shree Lekha Kandasamy 和希克曼高中學生 Saathvik Kannan 合作,分析了 200 多株猴痘病毒的 DNA 序列,病毒跨越數十年,從 1965 年病毒首次開始傳播,到 2000 年代初期的爆發,再到 2022 年再次爆發。

「透過時間分析,我們能夠看到病毒是如何隨時間進化的,一個關鍵的發現是病毒現在正在積累突變,特別是在藥物和疫苗抗體應該結合的地方」,Sachdev 說。「因此,病毒變得越來越聰明,它能夠避免被我們身體免疫反應的藥物或抗體所針對,並繼續傳播給更多人」。

大海撈針

近 30 年來,辛格一直在研究病毒學和 DNA 基因組複製。 他說,猴痘病毒的同源性或結構與牛痘病毒非常相似,牛痘病毒已被用作治療天花的疫苗。 這使 Singh 和他的合作者能夠創建一個準確的猴痘病毒蛋白質 3D 計算機模型,並確定特定突變的位置以及它們在導致病毒最近變得如此具有傳染性方面的作用。

「我們的重點是研究參與複制病毒基因組的特定基因,猴痘是一種巨大的病毒,基因組中大約有 200,000 個 DNA 鹼基」,辛格說。「猴痘的 DNA 基因組被轉化為近 200 種蛋白質,因此它配備了複製、分裂和繼續感染他人所需的所有『盔甲』。病毒會複制數十億個自身,只有適者生存,因為 這些突變幫助它們適應並繼續傳播。”

Kannan 和 Kandasamy 在分析猴痘病毒株時檢查了五種特定蛋白質:DNA 聚合酶、DNA 解旋酶、橋接蛋白 A22R、DNA 糖基化酶和 G9R。

「當他們向我發送數據時,我看到突變發生在影響 DNA 基因組結合的關鍵點,以及藥物和疫苗誘導抗體應該結合的地方」,辛格說。「這些因素肯定會導致病毒傳染性增加。這項工作很重要,因為解決問題的第一步是首先確定問題具體發生在哪裡,這是團隊的努力」。

病毒的進化

研究人員繼續質疑猴痘病毒是如何隨時間進化的。 目前 CDC 批准的治療猴痘的藥物的療效並不理想,這可能是因為它們最初是為治療 HIV 和皰疹而開發的,但後來獲得了緊急使用授權,以試圖控制最近的猴痘爆發。

「一種假設是,當患者接受這些藥物治療 HIV 和皰疹時,他們可能在不知情的情況下感染了猴痘,而猴痘病毒變得更聰明並發生變異以逃避藥物」,辛格說。「另一種假設是猴痘病毒可能會劫持我們體內的蛋白質,並利用它們變得更具傳染性和致病性」。

自 2020 年 COVID-19 大流行開始以來,Singh 和 Kannan 一直在合作,確定導致 COVID-19 變體的特定突變,包括 Delta 和 Omicron。 Kannan 最近因支持他們的「可持續發展目標」而獲得聯合國認可,該目標有助於應對世界上最大的挑戰。

辛格說:「如果沒有我的團隊成員,我不可能完成這項研究,我們的努力幫助科學家和藥物開發人員協助應對這些病毒爆發,因此參與其中是值得的」。

「痘病毒複製複合物的突變:2022 年爆發的潛在促成因素」最近發表在《自體免疫雜誌》上。 該研究的共同作者包括 Shrikesh Sachdev、Athreya Reddy、Shree Lekha Kandasamy、Siddappa Byrareddy、Saathvik Kannan 和 Christian Lorson。

 

更多信息:Saathvik R. Kannan et al,猴痘病毒複製複合體中的突變:2022 年爆發的潛在促成因素,自體免疫雜誌 (2022)。 DOI:10.1016/j.jaut.2022.102928

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Monkeypox mutations cause virus to spread rapidly, evade drugs and vaccines, study finds

 University of Missouri / NOVEMBER 4, 2022

 

 

Credit: University of Missouri

Monkeypox has infected more than 77,000 people in more than 100 countries worldwide, and—similar to COVID-19—mutations have enabled the virus to grow stronger and smarter, evading antiviral drugs and vaccines in its mission to infect more people.

Now, a team of researchers at the University of Missouri have identified the specific mutations in the monkeypox virus that contribute to its continued infectiousness. The findings could lead to several outcomes: modified versions of existing drugs used to treat people suffering from monkeypox or the development of new drugs that account for the current mutations to increase their effectiveness at reducing symptoms and the spread of the virus.

Kamlendra Singh, a professor in the MU College of Veterinary Medicine and Christopher S. Bond Life Sciences Center principal investigator, collaborated with Shrikesh Sachdev, Shree Lekha Kandasamy and Hickman High School student Saathvik Kannan, to analyze the DNA sequences of more 200 strains of monkeypox virus spanning multiple decades, from 1965, when the virus first started spreading, to outbreaks in the early 2000s and again in 2022.

“By doing a temporal analysis, we were able to see how the virus has evolved over time, and a key finding was the virus is now accumulating mutations specifically where drugs and antibodies from vaccines are supposed to bind,” Sachdev said. “So, the virus is getting smarter, it is able to avoid being targeted by drugs or antibodies from our body’s immune response and continue to spread to more people.”

Needles in a haystack

Singh has been studying virology and DNA genome replication for nearly 30 years. He said the homology, or structure, of the monkeypox virus is very similar to the vaccinia virus, which has been used as a vaccine to treat smallpox. This enabled Singh and his collaborators to create an accurate, 3D computer model of the monkeypox virus proteins and identify both where the specific mutations are located and what their functions are in contributing to the virus becoming so infectious recently.

“Our focus is on looking at the specific genes involved in copying the virus genome, and monkeypox is a huge virus with approximately 200,000 DNA bases in the genome,” Singh said. “The DNA genome for monkeypox is converted into nearly 200 proteins, so it comes with all the ‘armor’ it needs to replicate, divide and continue to infect others. Viruses will make billions of copies of itself and only the fittest will survive, as the mutations help them adapt and continue to spread.”

Kannan and Kandasamy examined five specific proteins while analyzing the monkeypox virus strains: DNA polymerase, DNA helicase, bridging protein A22R, DNA glycosylase and G9R.

“When they sent me the data, I saw that the mutations were occurring at critical points impacting DNA genome binding, as well as where drugs and vaccine-induced antibodies are supposed to bind,” Singh said. “These factors are surely contributing to the virus’ increased infectivity. This work is important because the first step toward solving a problem is identifying where the problem is specifically occurring in the first place, and it is a team effort.”

The evolution of viruses

Researchers continue to question how the monkeypox virus has evolved over time. The efficacy of current CDC-approved drugs to treat monkeypox have been suboptimal, likely because they were originally developed to treat HIV and herpes but have since received emergency use authorization in an attempt to control the recent monkeypox outbreak.

“One hypothesis is when patients were being treated for HIV and herpes with these drugs, they may have also been infected with monkeypox without knowing, and the monkeypox virus got smarter and mutated to evade the drugs,” Singh said. “Another hypothesis is the monkeypox virus may be hijacking proteins we have in our bodies and using them to become more infectious and pathogenic.”

Singh and Kannan have been collaborating since the COVID-19 pandemic began in 2020, identifying the specific mutations causing COVID-19 variants, including Delta and Omicron. Kannan was recently recognized by the United Nations for supporting their ‘Sustainable Development Goals,’ which help tackle the world’s greatest challenges.

“I could not have done this research without my team members, and our efforts have helped scientists and drug developers assist with these virus outbreaks, so it is rewarding to be a part of it,” Singh said.

“Mutations in the monkeypox virus replication complex: Potential contributing factors to the 2022 outbreak” was recently published in Journal of Autoimmunity. Co-authors on the study include Shrikesh Sachdev, Athreya Reddy, Shree Lekha Kandasamy, Siddappa Byrareddy, Saathvik Kannan and Christian Lorson.

More information: Saathvik R. Kannan et al, Mutations in the monkeypox virus replication complex: Potential contributing factors to the 2022 outbreak, Journal of Autoimmunity (2022). DOI: 10.1016/j.jaut.2022.102928

 

 

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