【解説】新型コロナの治療薬やワクチン、現在の開発状況は？

【ワシントンＡＦＰ＝時事】新型コロナウイルスの治療薬やワクチンの開発を、世界中の製薬会社や研究所施設が急ピッチで進めている。異なる技術を利用して市場投入を目指す薬品をいくつか紹介する。（写真は資料写真）

■ギリアド・サイエンシズ
開発企業：米製薬ギリアド・サイエンシズ
開発対象：治療薬
実用化時期：今年後半

　ギリアドの抗ウイルス薬「レムデシビル」は、新型コロナウイルス感染症（ＣＯＶＩＤ-１９）を引き起こすウイルスに関連した薬剤としては市場への投入が最も近いと考えられている。実際には、レムデシビル自体は以前からある薬剤で、エボラウイルス（エボラには効果がないことが証明された）など新型コロナとは別のウイルスを念頭に開発されたものだが、まだどの疾患に対しても承認が得られていない。
　それでも医師らによると、レムデシビルは中国の新型コロナウイルス感染患者の一部に対する治療において、早期の有望性を示しているという。ギリアドは現在、アジア地域で最終段階の臨床試験（第３相として知られる）が進められている。また、米国でもこれまでに少なくとも１人の患者の治療に使用された。
　世界保健機関（ＷＨＯ）事務局長上級顧問のブルース・エイルワード氏は、中国で最近開かれた記者会見で「実質的な有効性を持つ可能性があると考えられる薬剤は現時点でひとつしかない。それはレムデシビルだ」と述べている。

■モデルナ
開発企業：米製薬モデルナ
開発対象：ワクチン
実用化時期：１２～１８か月後

　中国の研究者らによって新型コロナウイルスのゲノム（全遺伝情報）が公開されてからほどなくして、新型コロナウイルスがヒト細胞に結合して感染する際に用いる部位「スパイクタンパク質」の再現モデルを米テキサス大学オースティン校のチームが作成した。チームは、極低温電子顕微鏡法を用いてこれの画像化にも成功している。
　そして、有害な影響を及ぼすことなく人体の免疫反応を引き起こす可能性があるこの再現モデルそのものが、ワクチン候補の基盤となった。これはワクチン開発のための古典的手法で、その始まりは１７９６年の天然痘ワクチンとされている。
　２０１０年に設立された比較的新しい企業であるモデルナはまた、米国立衛生研究所とも協力してワクチン開発に取り組んでいる。このワクチンはメッセンジャーＲＮＡを利用するもので、遺伝情報を用いてヒト筋肉組織内でスパイクタンパク質を生成させることから、体外で生成したタンパク質を接種する必要がない。
　テキサス大オースティン校のチームを率いたジェイソン・マクレラン氏は、「迅速なプロセス」がこの手法の長所であると述べ、体外でタンパク質を生成する従来型のアプローチは調整が難しく、長い時間がかかると説明した。
　このＲＮＡワクチンはマウス実験による有効性が確認された後、３月１６日に初のヒト臨床試験が開始された。

■リジェネロン・ファーマシューティカルズ
開発企業：米リジェネロン・ファーマシューティカルズ
開発対象：治療薬とワクチン
実用化時期：詳細なスケジュールは未公開

　リジェネロンは２０１９年、「モノクローナル抗体」を用いて静注薬剤を開発した。この薬剤はエボラ出血熱患者の生存率を著しく上昇させることが示されている。
　同社研究担当副責任者であるクリストス・キラトソウス氏は、ＡＦＰの取材でこの薬剤を開発するための手順を次のように説明した。
　まず人間に似た免疫系を持つよう遺伝子操作したマウスを作製し、そのマウスを生きたウイルスや弱毒化したウイルスに暴露させてヒト抗体をつくる。次にマウスが産生した抗体を単離し、最も効力が高いものを選別、それを実験室内で培養・精製する。それが人に静脈内投与される。

■サノフィ
開発企業：仏サノフィ
開発対象：ワクチン
実用化時期：未定

　サノフィは、米政府と提携して「組み換えＤＮＡプラットフォーム」と呼ばれる技術を活用したワクチン候補の開発を進めている。
　サノフィのワクチン開発では、新型コロナウイルスのＤＮＡを無害なウイルスのＤＮＡと組み合わせて、免疫反応を引き起こすキメラを作製する。
　この技術はすでに、サノフィのインフルエンザワクチンの基盤となっている。

■イノビオ・ファーマシューティカルズ
開発企業：米イノビオ・ファーマシューティカルズ
開発対象：ワクチン
実用化時期：年末までに緊急供給か

　米製薬イノビオは１９８０年代に設立されて以来、ＤＮＡワクチンの開発に取り組んでいる。ＤＮＡワクチンは、上で説明したＲＮＡワクチンと同様の方法で機能するが、連鎖のより早い段階で作用する。

■その他
　マラリアに効果のあるキニーネの構造を基に開発された合成薬「クロロキン」といった薬品についても、新型コロナウイルスに有効である可能性があり、科学者らはさらなる調査の必要性を訴えている。【翻訳編集ＡＦＰＢＢＮｅｗｓ】

〔ＡＦＰ＝時事〕（2020/03/24-13:01）

Pharmaceuticals and research labs across the world are racing to find vaccines and treatments for the new coronavirus, using a variety of different technologies.
According to Benjamin Neuman, a virologist at Texas A&M University-Texarkana, immunizing against the pathogen is a long shot: There has never been a very successful human vaccine against any member of the coronavirus family.
This is going to be a lot of trial, a lot of error, but we have a lot of options to try, Neuman said.
Treatment could come sooner, with antiviral remdesivir showing early promise and already being used on an ad hoc basis before regulatory approval.
US President Donald Trump has urged his scientists and drug companies to speed up the process -- but experts say fundamental constraints could leave little wiggle room.
A vaccine has to have a fundamental scientific basis. It has to be manufacturable. It has to be safe. This could take a year and a half -? -- or much longer, wrote H. Holden Thorp, the editor-in-chief of the journal Science in response to the president's calls.
Pharmaceutical executives have every incentive to get there quickly -- they will be selling the vaccine after all -? but thankfully, they also know that you can't break the laws of nature to get there.
The United States is funding several companies through the Department of Health and Human Services (HHS) and National Institutes of Health (NIH).
The Coalition for Epidemic Preparedness Innovations (CEPI), a global organization based in Oslo, is also helping to fund many companies, mostly smaller partners that would lack the capacity to scale-up mass production. It has so far provided about $24 million.
- Firm: Gilead sciences -

What it is: Treatment
When it might come: Later this year
Of all the drugs linked to the virus that causes COVID-19, Gilead's remdesivir could be the closest to market launch. It's actually not new per se but was developed to fight other viruses including Ebola (where it was shown to be ineffective) and it hasn't yet been approved for anything.
Still, it has shown early promise in treating some coronavirus patients in China, according to doctors, and Gilead is moving ahead with final stage clinical trials in Asia (known as Phase 3). It has also been used to treat at least one US patient so far.
NIH's Anthony Fauci, one of the top government scientists overseeing the coronavirus response, has said it could be available in the next several months.
There's only one drug right now that we think may have real efficacy. And that's remdesivir, said Bruce Aylward, a World Health Organization official at a recent press conference in China.
Remdesivir gets modified inside the human body to become similar to one of the four building blocks of DNA, called nucleotides.
Neuman told AFP that when viruses copy themselves, they do it quickly and a bit sloppily, meaning they might incorporate remdevisir into their structure -- though human cells, which are more fastidious, won't make the same mistake.
If the virus incorporates the remdesivir into itself, the drug adds unwanted mutations that can destroy the virus.
- Firm: Moderna -
What it is: Vaccine
When it might come: 12-18 months
Within weeks of Chinese researchers making the genome of the virus public, a team at the University of Texas at Austin was able to create a replica model of its spike protein, the part which attaches to and infects human cells, and image it using a cryogenic (cooled) electron microscope.
This replica itself is now the basis for a vaccine candidate because it may provoke an immune response in the human body without causing harm -- the classical method for developing vaccines based on principles dating back to smallpox vaccine in 1796.
NIH is also working with Moderna, a relatively new firm founded in 2010, to make a vaccine using the protein's genetic information to grow it inside human muscle tissue, rather than having to inject it in.
This information is stored in an intermediary transient substance called messenger RNA that carries genetic code from DNA to cells.
The advantage is that it's really fast, explained Jason McLellan, who led the UT Austin team, whereas the traditional approach of creating the protein outside is difficult to scale and takes a long time.
The vaccine began its first human trial on March 16 after being proven effective in mice.
If all goes to plan, it could be available on the market in about a year and a half, ready in case the coronavirus outbreak continues until the next flu season, according to Fauci.
- Firm: Regeneron -
What it is: Treatment and vaccine
When it might come: Firm timeline not yet provided
Regeneron last year developed an intravenous drug that was shown to significantly boost survival rates among Ebola patients using what are known as monoclonal antibodies.
To do this, they genetically modified mice to give them human-like immune systems. The mice are exposed to viruses, or weakened forms of them, in order to produce human antibodies, Christos Kyratsous, the company's vice president of research told AFP.
These antibodies are then isolated and screened to find the most potent ones, which are grown in labs, purified and given to humans intravenously.
If everything goes well, we should know what our best antibodies are within the next few weeks, with human trials to begin by summer, said Kyratsous.
The drug could work as both a treatment and as a vaccine, by dosing up people before they are exposed -- though these effects would be only temporary.
In the near term, they are also trying to repurpose another of their drugs devised using the same platform called Kevzara, which is approved to treat inflammation caused by arthritis.
This could help fight the lung inflammation seen in the severe forms of the COVID-19 disease -- in other words fighting a symptom as opposed to the virus itself.
- Firm: Sanofi -
What it is: Vaccine
When it might come: Time not yet clear
The French drugmaker is partnering with the US government to use a so-called recombinant DNA platform to produce a vaccine candidate.
It takes the virus' DNA and combines it with DNA from a harmless virus, creating a chimera that can provoke an immune response.
The antigens it produces can then be scaled up.
The technology is already the basis of Sanofi's influenza vaccine, and believes it has a head start due to a SARS vaccine it developed that offered partial protection in animals.
David Loew, the company's head of vaccines, is reported to have said Sanofi expects to have a research candidate ready for lab testing within six months and for clinical study within a year and a half.
- Firm: Inovio Pharmaceuticals -
What it is: Vaccine
When it might come: Emergency supplies by end of year?
Inovio, another US biopharmaceutical, has since its founding in the 1980s worked on DNA vaccines -- which work in a similar way to RNA vaccines explained above but work at an earlier link of the chain.
As an analogy, DNA can be thought of as a reference book in a library, while RNA is like a photocopy of a page from that book containing instructions to carry out a task.
We plan to begin human clinical trials in the US in April and soon thereafter in China and South Korea, where the outbreak is impacting the most people, said J. Joseph Kim, Inovio's president and CEO in a statement.
We plan on delivering one million doses by year end with existing resources and capacity.
- Other notable efforts -
British drugmaker GlaxoSmithKline has teamed up with a Chinese biotech firm, providing adjuvant platform technology.
An adjuvant is added to some vaccines to enhance the immune response, thereby creating a stronger and longer lasting immunity against infections than the vaccine alone.
Like Moderna, CureVac is working with the University of Queensland on a messenger RNA vaccine. Its CEO Daniel Menichella met with the White House earlier this month, and announced the company expects to have a candidate within a few months.
American pharma Johnson & Johnson is looking at repurposing some of its existing drugs to see how they might help treat the symptoms of patients already infected with the virus.
It's also working on developing a vaccine involving a deactivated version of the pathogen.
California-based Vir biotechnology has isolated antibodies from SARS survivors and is looking to see if these can treat the new coronavirus. Its platform has previously developed treatments for Ebola and other diseases.
Even the likes of chloroquine -- the synthetic form of quinine, used to treat malaria, may have some properties that fight the virus and scientists are calling for more work to investigate.