Tajik officials said on Monday that the cyclists, who were touring the former Soviet country, had been attacked with knives and firearms after being rammed by the auto, which indicated that the deaths were a result of murder.
The cyclists were travelling on a road that adjoins the famous Pamir Highway, a Soviet-era road surrounded by stunning mountain scenery. The other three cyclists - also believed to be foreigners - were treated for minor injuries.
A State Department official said it was not yet identifying the victims, and referred questions on the incident to local authorities. Tajik President Emomali Rahmon sent the leaders of each country a telegram expressing condolences Monday.
Two of the victims were American, one was Swiss, and another was from the Netherlands, foreign and Tajik officials said. The Ministry blamed the Islamic Renaissance Party of Tajikistan (IRPT) for the attack.
Two suspects in the case were killed after they "resisted arrest" and a further four have been detained, the minister said.
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'(The suspects) had knives and firearms, ' said interior minister Ramazon Hamro Rahimzoda, adding that two other cyclists, Swiss and Dutch nationals, were injured and hospitalised.
A purported video of the incident published online by Radio Free Europe and credited to an anonymous source showed a vehicle doing a U-turn on a narrow road after it had already knocked down a group of cyclists and then running over a few of them again.
"We strongly condemn the cruelty of the attackers and recognise that they in no way represent the kindness and hospitality of the Tajik people", it said in a statement.
The allegation comes after ISIL, on Monday, claimed a "detachment from the soldiers of the Caliphate" carried out the attack against "citizens of Crusader coalition countries" without offering details or evidence of their involvement.
Swiss Foreign Ministry spokeswoman Silvia Mueller said that while the circumstances of the crash were unclear, the Swiss government's travel advice for Tajikistan notes there is a risk of attacks and poor road travel conditions in the Central Asian country.
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Western tourists killed in Tajikistan
Tajikistan is one of the poorest of the former Soviet states and has been battling against the spread of radical Islam for years. The mountains and valleys of Central Asia are an enticing but sometimes unsafe destination for adventure travellers.